Metabolism and Health

Two siblings showed increased galactose and galactose-related metabolites in neonatal screening. Diagnostic workup did not reveal abnormalities in any of the known disease-causing enzymes involved in galactose metabolism. Using whole-exome sequencing, we identified a homozygous missense variant in PPA1 encoding the cytosolic pyrophosphatase 1 (PPA1), c.557C>T (p.Thr186Ile). The enzyme activity of PPA1 was determined using a colorimetric assay, and the protein content was visualized via western blotting in skin fibroblasts from one of the affected individuals. The galactolytic activity of the affected fibroblasts was determined by measuring extracellular acidification with a Seahorse XFe96 analyzer. PPA1 activity decreased to 22% of that of controls in the cytosolic fraction of homogenates from patient fibroblasts. PPA1 protein content decreased by 50% according to western blot analysis, indicating a reduced stability of the variant protein. The extracellular acidification rate was reduced in patient fibroblasts when galactose was used as a substrate. Untargeted metabolomics of blood samples revealed an elevation of other metabolites related to pyrophosphate metabolism. Besides hyperbilirubinemia in the neonatal period in one child, both children were clinically unremarkable at the ages of 3 and 14 years, respectively. We hypothesize that the observed metabolic derangement is a possible mild manifestation of PPA1 deficiency. Unresolved abnormalities in galactosemia screening might result in the identification of more individuals with PPA1 deficiency, a newly discovered inborn metabolic disorder (IMD). Full article

Obesity has become a global epidemic, contributing to the development of numerous chronic diseases, including diabetes, chronic kidney disease (CKD) and cardiovascular disorders. MicroRNAs (miRNAs) have emerged as key regulators in various biological processes, including metabolism, inflammation, and tissue remodeling, making them pivotal players in obesity-related pathologies. This review aims to provide comprehensive insights into the roles of miRNAs in obesity, with a particular emphasis on their involvement in the pathogenesis of CKD and cardiovascular disorders. We highlight the involvement of specific miRNAs in adipose tissue development, energy homeostasis, inflammation, and insulin resistance, contributing to the pathogenesis of obesity. Moreover, we explore the impact of miRNAs on renal fibrosis and inflammation, giving clues on their roles in the development and progression of CKD. Additionally, we discuss the influence of miRNAs on endothelial dysfunction, atherosclerosis, and cardiac remodeling, emphasizing their contribution to obesity-related cardiovascular disorders. Understanding the regulatory functions of miRNAs in these interconnected conditions holds promise for improved diagnosis, prognosis, and therapeutic interventions. Indeed, miRNAs are potential diagnostic biomarkers for obesity-related diseases, although challenges remain to be elucidated before their clinical translation. Furthermore, we highlight the emerging strategies that target miRNAs as therapeutic interventions to mitigate the detrimental effects of obesity on kidney and cardiovascular health. Full article

Dark tea has great potential in regulating glycolipid metabolism, and theabrownin (TB) is considered to be the characteristic and bioactive constituent of dark tea. This study evaluated the ability of TB1 (fermented for 7 days) and TB2 (fermented for 14 days) isolated from dark tea to reverse insulin resistance (IR) in HepG2 cells. The results indicated that TB significantly ameliorated oxidative stress by improving mitochondrial function. In addition, TB improved glycogen synthesis and glucose consumption, and inhibited gluconeogenesis and fatty acid synthesis, by regulating GSK3β (Glycogen synthase kinase 3β), G6Pase (Glucose-6-phosphatase), GCK (Glucokinase), PEPCK1 (Phosphoenolpyruvate carboxy kinase 1), SREBP-1C (sterol regulatory element-binding protein 1C), FASN (fatty acid synthase), and ACC (Acetyl-CoA carboxylase). Additionally, the results of Western blot and real-time PCR experiments demonstrated that TB modulated glucolipid metabolism through the IRS-1 (Insulin receptor substrate 1)/PI3K (phosphatidylinositol-3 kinase)/Akt (protein kinase B) signaling pathway. Treatment with the PI3K inhibitor demonstrated a favorable correlation between PI3K activation and TB action on glycolipid metabolism. Notably, we observed that TB2 had a greater effect on improving insulin resistance compared with TB1, which, due to its prolonged fermentation time, increased the degree of oxidative polymerization of TB. Full article

Obesity and diabetes mellitus epidemics exert a measurable impact on the liver transplant (Ltx) population. This study aimed to investigate the metabolic profile of Ltx recipients and its association with body fat distribution. Adults who underwent de novo elective cadaveric-donor Ltx were eligible. Metabolic syndrome (MS) was diagnosed based on the adapted International Diabetes Federation, the American Heart Association, and the National Heart, Lung, and Blood Institute guidelines. We recruited 100 patients with a mean age of 54 years, of whom 70% were men. Overall, 54% met the criteria for MS, most of which comprised new-onset cases. Excessive fat accumulation in liver donors was found to be associated with an increased metabolic risk in liver recipients. Haemoglobin A1C (OR: 8.962, 95% CI: 2.188–84.545, p = 0.013), ferritin (OR: 1.024, 95% CI: 1.005–1.054, p = 0.038), and de novo hypertriglycaeridemia (OR 27.957, 95% CI: 2.626–752.121, p = 0.014) were found to be independently associated with de novo MS. After a step-wise multivariate analysis, only the anthropometric obesity indices were significantly associated with abdominal fat distribution in Ltx recipients. Metabolic complications were common in liver recipients. Both pre- and post-Ltx factors impacted MS development in liver recipients and determined abdominal fat distribution. Full article

Grape consumption acts on the immune system to produce antioxidant and anti-inflammatory effects. Since immune activity demonstrates circadian rhythmicity, with peak activity occurring during waking hours, the timing of grape intake may influence the magnitude of its antioxidant effect. This study followed a 2 × 2 factorial randomized, controlled design wherein healthy men and women (n = 32) consumed either a grape or placebo drink with a high-fat meal in the morning or evening. Urine was collected for measurements of biomarkers of oxidative stress and grape metabolites at baseline and post-meal at hour 1 and hours 1–6. F-2 isoprostane levels showed main effects of time period (baseline < hour 1 < hours 1–6, p < 0.0001), time (a.m. > p.m., p = 0.008) and treatment (placebo > grape, p = 0.05). Total F2-isoprostane excretion expressed as % baseline was higher in the a.m. vs. p.m. (p = 0.004) and in the a.m. placebo vs. all other groups (p < 0.05). Tartaric acid and resveratrol excretion levels were higher in the grape vs. placebo group (p < 0.05) but were not correlated with F-2 isoprostane levels. The findings support a protective effect of grape consumption against morning sensitivity to oxidative stress. Full article

The thyroid hormones (THs) regulate various physiological mechanisms in mammals, such as cellular metabolism, cell structure, and membrane transport. The therapeutic drugs propylthiouracil (PTU) and phenytoin are known to induce hypothyroidism and decrease blood thyroid hormone levels. To analyze the impact of these two drugs on systemic metabolism, we focused on metabolic changes after treatment. Therefore, in a rat model, the metabolome of thyroid and liver tissue as well as from the blood plasma, after 2-week and 4-week administration of the drugs and after a following 2-week recovery phase, was investigated using targeted LC-MS/MS and GC-MS. Both drugs were tested at a low dose and a high dose. We observed decreases in THs plasma levels, and higher doses of the drugs were associated with a high decrease in TH levels. PTU administration had a more pronounced effect on TH levels than phenytoin. Both drugs had little or no influence on the metabolomes at low doses. Only PTU exhibited apparent metabolome alterations at high doses, especially concerning lipids. In plasma, acylcarnitines and triglycerides were detected at decreased levels than in the controls after 2- and 4-week exposure to the drug, while sphingomyelins and phosphatidylcholines were observed at increased levels. Interestingly, in the thyroid tissue, triglycerides were observed at increased concentrations in the 2-week exposure group to PTU, which was not observed in the 4-week exposure group and in the 4-week exposure group followed by the 2-week recovery group, suggesting an adaptation by the thyroid tissue. In the liver, no metabolites were found to have significantly changed. After the recovery phase, the thyroid, liver, and plasma metabolomic profiles showed little or no differences from the controls. In conclusion, although there were significant changes observed in several plasma metabolites in PTU/Phenytoin exposure groups, this study found that only PTU exposure led to adaptation-dependent changes in thyroid metabolites but did not affect hepatic metabolites. Full article

Background: Previous evidence yielded contradictory findings on the relationship between metformin and anemia. This study aims to assess whether metformin use is associated with iron-deficiency anemia (IDA) risk in patients with type 2 diabetes (T2D) in Beijing, China. Methods: Overall, 60,327 newly diagnosed T2D patients were included based on a historical cohort study design. The information pertaining to these patients was gathered from the Beijing Medical Claim Data for Employees Database. These patients were then categorized into the metformin and non-metformin groups and matched on a 1:1 propensity score based on their initial antidiabetic prescription. The Cox proportional hazards models were utilized to calculate the incidences and the hazard ratios (HRs). Results: The study enrolled 27,960 patients with type 2 diabetes, with 13,980 patients in each of the initial glucose-lowering prescription groups: metformin and non-metformin. During a median follow-up period of 4.84 years, 4832 patients developed IDA. The incidence of IDA was significantly lower in the metformin group (26.08/1000 person-years) than in the non-metformin group (43.20/1000 person-years). Among the three groups divided by the proportion of days covered by metformin, we found a negative correlation between the proportion of days covered by metformin and the risk of IDA. The risk of IDA in patients with a proportion of days covered by metformin of <20%, 20–79%, and ≥80% was 0.43 (0.38, 0.48), 0.37 (0.34, 0.42), and 0.91 (0.85, 0.98), respectively, compared to the non-metformin group. We also performed subgroup analyses and sensitivity analyses: the incidence of IDA in the metformin group was lower than that in the non-metformin group in all subgroups, and the protective effect was more significant in subgroups of patients aged ≥65, with Charlson comorbidity index (CCI) ≥2, and with gastric acid inhibitor use. Conclusions: In Chinese patients with T2DM, metformin treatment was associated with a decreased risk of IDA admission, and this risk responded positively to the proportion of days covered by metformin. These findings suggest that metformin may have a pleiotropic effect on IDA in patients with type 2 diabetes. Our study has important clinical implications for the management of patients with diabetes and other conditions that increase the risk of IDA. Full article

(1) Background: Design thinking, as a human-centered design method, represents a unique framework to support the planning, testing, and evaluation of new clinical spaces for diabetic care throughout all phases of construction. This approach prioritizes the needs and experiences of diabetic patients to create innovative and effective healthcare environments. By applying design-thinking principles, healthcare facilities can optimize the design and functionality of their clinical spaces, ensuring a patient-centered approach to diabetic care. This holistic and personalized approach can ultimately enhance the overall quality of diabetic care provided to patients. (2) Methods: The study used the action research method and progressively explored diabetes patients’ needs and preferences for care, subsequently developing creative solutions to achieve the goals. There were six doctors, seven nursing staffs, four case managers and three family members who participated in the design-thinking workshop. (3) Results: The participating trainees in this study developed unique and innovative solutions during the iterative process of “divergent thinking” and “focused thinking”, including diabetes dietary guidelines for food ordering and delivery platforms, and the design of accompanying health-education picture books to enable patients to learn the care process and precautions before, during, and after discharge. (4) Conclusions: This continuing education model promoted sharing among participants, improved collaboration and mutual learning, and increased motivation through goal setting. Full article

Background: The aim of this study was to determine the phagocytic activity of thrombocytes in patients with gastric cancer and to assess the effect of oral and parenteral preoperative glutamine-based immunonutrition on nutritional status, thrombocyte phagocytic activity, and early postoperative outcomes. Methods: Patients suffering from invasive gastric cancer had been treated with preoperative immunonutrition with glutamine, and they were compared to patients without nutritional treatment. Nutritional status, percentage of weight loss, and BMI were assessed. Levels of total protein, albumin, cholesterol, triglycerides, platelets, and their phagocytic ability were measured twice. Postsurgical complications were assessed via the Clavien–Dindo classification. Results: Group I consisted of 20 patients with an oral glutamine—10 g daily. Group II had 38 patients who received intravenous glutamine, 1.5 mL per kg body weight of Dipeptiven. Group III consisted of 25 patients who did not receive preoperative immunonutrition. In total, 47% of patients in Group I, 54% of patients in Group II, and 33% of patients in Group III were malnourished. In Group I, the percentage of phagocytizing platelet (%PhP) was 1.1 preoperatively and 1.2 postoperatively. The phagocytic index (PhI) was 1.0 and 1.1. In Group II, %PhP was 1.1 and 1.2 and PhI was 1.0 and 1.1. In Group III, the %PhP was 1.0 and 1.2 and PhI was 1.0 and 1.1. An increase in triglyceride level was observed in both immunonutrition groups. There was a decline in total protein and albumin level in Group II. In Group III, there was a decline in total protein, albumin, and cholesterol level. The total platelet count and PhI were increased in both immunonutrition groups. There was also a rise in %PhP in Group II. In Group III, there was a rise in blood platelet level, %PhP, and PhI. The complication rates were 53% in Group I, 29% in Group II, and 40% in Group III. Conclusions: In invasive gastric cancer, laboratory nutritional parameters are significantly reduced, causing malnutrition in 44.7% of patients. Oral glutamine supplementation inhibited the postoperative decline in protein metabolism parameters; however, this did not affect the reduction in the percentage of postoperative complications. Glutamine used preoperatively significantly reduced the percentage of serious surgical complications, regardless of the way it was supplemented. Patients with invasive gastric cancer have a significant decrease in platelet phagocytic activity. The administered preoperative parenteral nutrition and the surgical procedure itself influenced the improvement of the phagocytic activity of blood platelets. Glutamine did not have this effect, regardless of the route of administration. Full article

Cardiovascular disease and type 2 diabetes mellitus are leading contributors to the health inequity experienced by Aboriginal and Torres Strait Islander peoples, and their antecedents can be identified from early childhood. We aimed to establish the quality of available data and the prevalence of cardiometabolic risk markers among Aboriginal and Torres Strait Islander children and youths (0–24-year-olds) to inform public health approaches. A systematic review of the peer-reviewed and grey literature was conducted between 1 January 2000–28 February 2021. Included studies reported population prevalence of cardiometabolic risks, including elevated blood pressure, obesity, central adiposity, dyslipidaemia, hyperglycaemia, and ‘metabolic syndrome’ for Aboriginal and Torres Strait Islander people aged 0–24 years. Fifteen studies provided population estimates. Data quality was limited by low response rates (10/15 studies) and suboptimal outcome measurements. Obesity is the most reported risk (13/15 studies). Aboriginal and Torres Strait Islander children have an excess risk of obesity from early childhood and prevalence increases with age: 32.1% of Aboriginal and Torres Strait Islander 18–24-year-olds had obesity and 50.8% had central adiposity. In a cohort of 486 9–14-year-olds in Darwin, 70% had ≥1 component of metabolic syndrome; 14% met the full criteria for the syndrome. The prevalence of cardiometabolic risk in Aboriginal and Torres Strait Islander young people is difficult to estimate due to limitations in measurement quality and sampling representativeness. Available data suggest that cardiometabolic risk markers are evident from early childhood. The establishment of national and state-level datasets and a core outcome set for cardiometabolic screening would provide opportunities for preventative action. Full article

Objective: To investigate gender and age-specific distribution patterns of cardiovascular disease risk factors in the Saudi population for tailored health policies. Methods: From the heart health promotion study, 3063 adult Saudis were included in this study. The study cohort was divided into five age groups (less than 40 years, 40–45 years, 46–50 years, 51–55 years and ≥56 years). The prevalence of metabolic, socioeconomic, and cardiac risk was compared between the groups. Anthropometric and biochemical data were gathered using the World Health Organization stepwise approach to chronic disease risk factors. The cardiovascular risk (CVR) was determined using the Framingham Coronary Heart Risk Score. Results: The prevalence of CVR risk increased with age in both genders. Both Saudi men and women exhibit similar propensities for sedentary lifestyles and unhealthy food habits. The prevalence of tobacco smoking was significantly higher and from an early age in males compared to females (28% and 2.7%, respectively, at age 18–29 years). There is no significant difference in either the prevalence of diabetes, hypertension, or metabolic syndrome between men and women before the age of 60 years. Old Saudi females (≥60 years) have a higher prevalence of diabetes (50% vs. 38.7%) and metabolic syndrome (55.9% versus 43.5%). Obesity was more prevalent in females aged 40–49 years onwards (56.2% vs. 34.9% males), with 62.9% of females aged ≥60 years being obese compared to 37.9% of males. Dyslipidaemia prevalence increased with the progression of age, significantly more in males than females. Framingham high-risk scores showed that 30% of males were at high risk of cardiovascular diseases at the age group of 50–59 years, while only 3.7% of the females were considered as such. Conclusions: Both Saudi men and women exhibit similar propensities for sedentary lifestyles and unhealthy food habits, with a marked increase in cardiovascular and metabolic risk factors with age. Gender differences exist in risk factor prevalence, with obesity as the main risk factor in women, while smoking and dyslipidaemia were the main risk factors in men. Full article

Metabolic syndrome (MetS) is related to depression and contributes to reduced life expectancy in individuals with mental disorders. Stress coping strategies are important factors in the development and maintenance of depressive disorders and have been related to metabolic disturbances. The aim of this study was to determine whether there is a difference in the use of positive (re- and devaluation, distraction, and control) and negative stress coping strategies in relation to patients’ MetS. A sample of 363 individuals (n female = 204, n male = 159) with a diagnosis of depression was measured with the Stress Coping Style Questionnaire and the Beck Depression Inventory. In addition, we collected data on MetS (waist circumference, triglycerides, high-density lipoprotein, fasting glucose/diabetes, blood pressure/hypertonia) according to the International Diabetes Federation. A 2 × 2 design including Mets (with vs. without) and sex (female vs. male) was performed to test for differences in stress coping strategies. Individuals with depression and MetS scored higher on distraction strategies than depressed individuals without MetS (p < 0.01, corrected with false discovery rate). In addition, we found sex differences in stress coping strategies indicating that women with depression scored higher on distraction strategies (p < 0.001, FDR corrected), as well as negative strategies (p < 0.001, FDR corrected), than men. No significant interaction between MetS and sex was found regarding the higher value of stress coping strategies. Findings suggest that individuals with depression and MetS used distraction strategies to a higher amount to cope with stress, which could be stress eating in some cases, than those without MetS. Women with depressive disorders had higher values than men on other coping strategies in our sample of individuals with depression. A better understanding of MetS and sex-specific differences in stress coping strategies might help to plan more effective preventive strategies and personalized treatment options for depression. Full article

Obesity has been linked to numerous health and nutritional problems, including impaired iron metabolism, a common cause of anemia. We aimed to determine the prevalence of anemia, iron deficiency (ID), and iron deficiency anemia (IDA) among women aged 20–49 years based on body mass index (BMI) status. We used measures of iron status and body mass index from the 2001–2006 National Health and Nutrition Examination Survey (NHANES). Mean serum ferritin, erythrocyte protoporphyrin, and soluble transferrin receptor were higher, while those of serum iron, percent transferrin saturation, and mean cell volume (MCV) were lower in women with obesity than those with normal weight (all p < 0.016). ID based on the ferritin model was 12.5 ± 1.0% vs. 22.9 ± 1.6% (p < 0.001); 9.0 ± 0.9% vs. 20.0 ± 1.3% (p < 0.001) based on the MCV model; and 8.1 ± 1.0% vs. 10.5 ± 1.2% (p > 0.05) based on the BII model for women with normal weight and women with obesity, respectively. Anemia prevalence was 5.5 ± 0.8% (normal) vs. 9.3 ± 1.0% (obese) (p = 0.005). The IDA estimates based on the ferritin and MCV models were similar but higher than that from the BII model (p < 0.001). Generally, the prevalence rates of ID and anemia (and IDA) were higher for women with obesity, but the method used to define deficiency mattered. The choice of iron indices is important for estimating ID and IDA in populations with obesity. Full article

As one of the OMICS in systems biology, metabolomics defines the metabolome and simultaneously quantifies numerous metabolites that are final or intermediate products and effectors of upstream biological processes. Metabolomics provides accurate information that helps determine the physiological steady state and biochemical changes during the aging process. To date, reference values of metabolites across the adult lifespan, especially among ethnicity groups, are lacking. The “normal” reference values according to age, sex, and race allow the characterization of whether an individual or a group deviates metabolically from normal aging, encompass a fundamental element in any study aimed at understanding mechanisms at the interface between aging and diseases. In this study, we established a metabolomics reference database from 20–100 years of age from a biracial sample of community-dwelling healthy men and women and examined metabolite associations with age, sex, and race. Reference values from well-selected healthy individuals can contribute to clinical decision-making processes of metabolic or related diseases. Full article

Prenatal stress alters fetal programming, potentially predisposing the ensuing offspring to long-term adverse health outcomes. To gain insight into environmental influences on fetal development, this QF2011 study evaluated the urinary metabolomes of 4-year-old children (n = 89) who were exposed to the 2011 Queensland flood in utero. Proton nuclear magnetic resonance spectroscopy was used to analyze urinary metabolic fingerprints based on maternal levels of objective hardship and subjective distress resulting from the natural disaster. In both males and females, differences were observed between high and low levels of maternal objective hardship and maternal subjective distress groups. Greater prenatal stress exposure was associated with alterations in metabolites associated with protein synthesis, energy metabolism, and carbohydrate metabolism. These alterations suggest profound changes in oxidative and antioxidative pathways that may indicate a higher risk for chronic non-communicable diseases such obesity, insulin resistance, and diabetes, as well as mental illnesses, including depression and schizophrenia. Thus, prenatal stress-associated metabolic biomarkers may provide early predictors of lifetime health trajectories, and potentially serve as prognostic markers for therapeutic strategies in mitigating adverse health outcomes. Full article

In vivo short echo time (TE) proton magnetic resonance spectroscopy (¹H-MRS) is a useful method for the quantification of human brain metabolites. The purpose of this study was to evaluate the performance of an in-house, experimentally measured basis set and compare it with the performance of a vendor-provided basis set. A 3T clinical scanner with 32-channel receive-only phased array head coil was used to generate 16 brain metabolites for the metabolite basis set. For voxel localization, point-resolved spin-echo sequence (PRESS) was used with volume of interest (VOI) positioned at the center of the phantoms. Two different basis sets were subjected to linear combination of model spectra of metabolite solutions in vitro (LCModel) analysis to evaluate the in-house acquired in vivo ¹H-MR spectra from the left prefrontal cortex of 22 healthy subjects. To evaluate the performance of the two basis sets, the Cramer-Rao lower bounds (CRLBs) of each basis set were compared. The LCModel quantified the following metabolites and macromolecules: alanine (Ala), aspartate (Asp), γ-amino butyric acid (GABA), glucose (Glc), glutamine (Gln), glutamate (Glu), glutathione (GHS), Ins (myo-Inositol), lactate (Lac), N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), taurine (Tau), phosphoryl-choline + glycerol-phosphoryl-choline (tCho), N-acetylaspartate + N-acetylaspartylglutamate (tNA), creatine + phosphocreatine (tCr), Glu + Gln (Glx) and Lip13a, Lip13b, Lip09, MM09, Lip20, MM20, MM12, MM14, MM17, Lip13a + Lip13b, MM14 + Lip13a + Lip13b + MM12, MM09 + Lip09, MM20 + Lip20. Statistical analysis showed significantly different CRLBs: Asp, GABA, Gln, GSH, Ins, Lac, NAA, NAAG, Tau, tCho, tNA, Glx, MM20, MM20 + Lip20 (p < 0.001), tCr, MM12, MM17 (p < 0.01), and Lip20 (p < 0.05). The estimated ratio of cerebrospinal fluid (CSF) in the region of interest was calculated to be about 5%. Fitting performances are better, for the most part, with the in-house basis set, which is more precise than the vendor-provided basis set. In particular, Asp is expected to have reliable CRLB (<30%) at high field (e.g., 3T) in the left prefrontal cortex of human brain. The quantification of Asp was difficult, due to the inaccuracy of Asp fitting with the vendor-provided basis set. Full article

Waist circumference is often used for the diagnosis of visceral obesity and metabolic syndrome. In Japan, obesity in women is defined by the government as a waist circumference of ≥90 cm and/or BMI of ≥25 kg/m². However, there has been a controversy for almost two decades as to whether waist circumference and its above-optimal cutoff are appropriate for the diagnosis of obesity in health checkups. Instead of waist circumference, the waist-to-height ratio has been recommended for the diagnosis of visceral obesity. In this study, the relationships between the waist-to-height ratio and cardiometabolic risk factors, including diabetes, hypertension and dyslipidemia, were investigated in middle-aged Japanese women (35~60 years) who were diagnosed as not having obesity according to the above Japanese criteria of obesity. The percentage of subjects showing normal waist circumference and normal BMI was 78.2%, and about one-fifth of those subjects (16.6% of the overall subjects) showed a high waist-to-height ratio. In subjects with normal waist circumference and normal BMI, odds ratios of high vs. not high waist-to-height ratio for diabetes, hypertension and dyslipidemia were significantly higher than the reference level. A considerable proportion of women who have a high cardiometabolic risk might be overlooked at annual lifestyle health checkups in Japan. Full article

Maternal obesity during pregnancy adversely impacts offspring health, predisposing them to chronic metabolic diseases characterized by insulin resistance, dysregulated macronutrient metabolism, and lipid overload, such as metabolic-associated fatty liver disease (MAFLD). Choline is a semi-essential nutrient involved in lipid and one-carbon metabolism that is compromised during MAFLD progression. Here, we investigated under high-fat (HF) obesogenic feeding how maternal choline supplementation (CS) influenced the hepatic lipidome of mouse offspring. Our results demonstrate that maternal HF+CS increased relative abundance of a subclass of phospholipids called plasmalogens in the offspring liver at both embryonic day 17.5 and after 6 weeks of postnatal HF feeding. Consistent with the role of plasmalogens as sacrificial antioxidants, HF+CS embryos were presumably protected with lower oxidative stress. After postnatal HF feeding, the maternal HF+CS male offspring also had higher relative abundance of both sphingomyelin d42:2 and its side chain, nervonic acid (FA 24:1). Nervonic acid is exclusively metabolized in the peroxisome and is tied to plasmalogen synthesis. Altogether, this study demonstrates that under the influence of obesogenic diet, maternal CS modulates the fetal and postnatal hepatic lipidome of male offspring, favoring plasmalogen synthesis, an antioxidative response that may protect the mouse liver from damages due to HF feeding. Full article

Background: Studies on the association between solute, nutrition and fluid intakes and mortality and later kidney function in critically ill acute kidney injury (AKI) patients receiving continuous veno-venous hemodialysis (CVVHD) are scarce. Methods: Altogether, 471 consecutive critically ill AKI patients receiving CVVHD in the research intensive care unit (ICU) were recruited in this single-center, retrospective study. Results: The median age was 66 (58–74) years, and 138 (29.3%) were female. The 90-day and one-year mortalities were 221 (46.9%) and 251 (53.3%), respectively. After adjusting for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE) score, coronary artery disease, immunosuppression, ICU care duration, mechanical ventilation requirement, vasopressor requirement and study time period, the cumulative daily intake of potassium, chloride, sodium, phosphate, calcium, glucose, lipids and water was associated with one-year mortality in separate multivariable cox proportional hazards models. In a sensitivity analysis excluding patients who died within the first three days of ICU care, the daily intake of chloride (hazard ratio (HR) 1.001, confidence interval (CI) 95% 1.000–1.003, p = 0.032), sodium (HR 1.001, CI 95% 1.000–1.002, p = 0.031) and calcium (HR 1.129, CI 95% 1.025–1.243, p = 0.014) remained independently associated with mortality within one-year in the respective, similarly adjusted multivariable cox analyses. The cumulative daily intake of chloride, sodium, calcium and water was independently associated with the estimated glomerular filtration rate (eGFR) at 90 days follow-up in separate substantially adjusted multivariable cox proportional hazards models. Conclusion: The cumulative daily intake of chloride, sodium and calcium is associated with mortality and daily chloride, sodium, calcium and water intake is associated with follow-up eGFR in critically ill patients with CVVHD-treated AKI. Full article

Background: Metabolic syndrome is characterized by cardiovascular and chronic disease risk factors that cause health problems. Inequalities in medical resources and information present a challenge in this context. Indigenous communities may be unaware of their risk for metabolic syndrome. Aims: This study explored factors associated with metabolic syndrome-related knowledge, attitudes, and behaviors among Taiwanese indigenous communities. Methods: For this descriptive cross-sectional survey, we collected anthropometric data and used a self-administered questionnaire between 1 July 2016, to 31 July 2017, from a convenience sample of an indigenous tribe in eastern Taiwan. The response rate was 92%. Results: The prevalence of metabolic syndrome was as high as 71%, and the average correct knowledge rate was 39.1%. The participants’ self-management attitudes were mainly negative, and the self-management behaviors were low in this population. Stepwise regression analysis showed that knowledge, attitude, age, perception of physical condition, and body mass index, which accounted for 65% of the total variance, were the most predictive variables for self-management behaviors. Conclusions: This is the first study to report the relationship between metabolic syndrome knowledge, attitudes, and behaviors in an indigenous population. There is an urgent need to develop safety-based MetS health education programs that can provide access to the right information and enhance self-management approaches to lessen the growing burden of MetS in indigenous communities. Full article

To date, most metabolomics biomarker research has focused on identifying disease biomarkers. However, there is a need for biomarkers of early metabolic dysfunction to identify individuals who would benefit from lifestyle interventions. Concomitantly, there is a need to develop strategies to analyse metabolomics data at an individual level. We propose “MetaboVariation”, a method that models repeated measurements on individuals to explore fluctuations in metabolite levels at an individual level. MetaboVariation employs a Bayesian generalised linear model to flag individuals with intra-individual variations in their metabolite levels across multiple measurements. MetaboVariation models repeated metabolite levels as a function of explanatory variables while accounting for intra-individual variation. The posterior predictive distribution of metabolite levels at the individual level is available, and is used to flag individuals with observed metabolite levels outside the 95% highest posterior density prediction interval at a given time point. MetaboVariation was applied to a dataset containing metabolite levels for 20 metabolites, measured once every four months, in 164 individuals. A total of 28% of individuals with intra-individual variations in three or more metabolites were flagged. An R package for MetaboVariation was developed with an embedded R Shiny web application. To summarize, MetaboVariation has made considerable progress in developing strategies for analysing metabolomics data at the individual level, thus paving the way toward personalised healthcare. Full article

In the general population, there is little evidence of a link between blood urea nitrogen (BUN) and long-term mortality. The goal of this study was to explore whether higher BUN concentration is a predictor of cardiovascular disease (CVD) and all-cause mortality. From 1999 to 2006, the National Health and Nutrition Examination Survey (NHANES) included 17,719 adult individuals. Death outcomes were ascertained by linkage to the database records through 31 December 2015. The Cox proportional hazard regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD and all-cause mortality in individuals. We also performed stratified analyses based on age, gender, drinking, smoking, history of hypertension and diabetes. During a mean follow-up 11.65 years, a total of 3628 deaths were documented, of which 859 were due to CVD. Participants with higher BUN had a higher risk of CVD and all-cause death compared to those with lower BUN. After multifactor adjustment for demographics, major lifestyle factors, and hypertension and diabetes history, higher BUN levels compared with lower levels were significantly associated with higher risk of CVD (HR: 1.48 [1.08, 2.02], P-trend < 0.001) and all-cause mortality (HR: 1.48 [1.28, 1.72], P-trend < 0.001). In subgroup analyses, we found that the trend in the association of BUN with the risk of death remained strong in female subjects. Greater BUN levels were linked to higher CVD and all-cause mortality in the NHANES of American adults. The importance of BUN in predicting death is supported by our research. Full article

Background: Metabolic syndrome (Met-S) is considered one of the most important health problems of the 21st century. It includes a group of metabolic disorders that increase the risk of cardiovascular diseases such as overweight and obesity, elevated lipid profile and blood pressure and insulin resistance (IR). Based on the information mentioned above in which there seems to be a relationship between IR and Met-S, the objective of this work was twofold: on the one hand, to assess the relationship between the values of different insulin resistance risk scales and Met-S determined with three different scales, and on the other, to determine whether any of the components of Met-S predispose more to the appearance of IR. Methods: A descriptive cross-sectional study of 418,343 workers. Waist circumference was measured and evaluated together with six formulas to assess the insulin resistance index. Categorical variables were evaluated by calculating the frequency and distribution of each one. For quantitative variables, mean and standard deviation were determined, and Student’s t-test was applied, while for qualitative variables, the chi-square test was performed. The usefulness of the different risk scales for insulin resistance for predicting metabolic syndrome was evaluated using ROC curves, the area under the curve (AUC), as well as their cut-off points for sensitivity, specificity, and the Youden index. Results: People with metabolic syndrome applying any criteria had higher values in the IR risk scales. The different IR scales made it possible to adequately classify people with metabolic syndrome. Of the three definitions of Met-S, the one that showed the greatest relationship with IR was IDF. Conclusions: Most risk scales for insulin resistance enable the presence of metabolic syndrome to be adequately classified, finding the best ones if the International Diabetes Federation (IDF) criteria are applied. Of the elements included in the Met-S, the one that seems to increase the risk of presenting IR the most is waist circumference; hence, the Met-S definition that is most related to IR is that of the IDF, which is the only one of the three in which a high value of waist circumference is necessary to be able to diagnose Met-S. Waist circumference can be considered the central essential component for detecting insulin resistance and, therefore, the early detection of metabolic syndrome. Full article

The aim of this study was to investigate the changes in bone marrow fatty acids early after ovariectomy-induced osteoporosis in rats, and explore the potential function of the bone marrow fatty acids. Ninety-six female Sprague Dawley rats (12 weeks) were randomly divided into an ovariectomized (OVX) group and Sham group (N = 48/group) and received ovariectomy or Sham surgery, respectively. After 3, 5, 7,14, 21 and 28 days, eight rats in each group were sacrificed to detect the composition of bone marrow fatty acids by means of gas chromatography-mass spectrometry and evaluate the trabecular bone microarchitecture by means of microCT. Bone marrow rinsing fluid and serum were collected for the detection of nitric oxide synthase/nitric oxide (NOS/NO) and bone metabolism related parameters, respectively. Our results demonstrated that the bone microstructure was damaged significantly from 14 days after OVX surgery onwards. Sample clustering and group separation were observed between the OVX group and Sham group 3 and 14 days after surgery, which suggested the role of bone marrow fatty acids in the early stage of postmenopausal osteoporosis. Palmitoleate, myristate and arachidonate were found to play an important role in classification between the OVX group and Sham group on the 3rd day after surgery (VIP > 1, p < 0.05). Palmitoleate, myristate, alpha linolenate, stearate and eicosenoate were found to play an important role in classification between the OVX group and Sham group on the 14th day after surgery (VIP > 1, p < 0.05). The levels of myristate, palmitoleate, alpha linolenate and eicosenoate were significantly decreased in the OVX group, while the levels of arachidonate and stearate were significantly increased in OVX group (p < 0.05). Additionally, myristate, palmitoleate, alpha linoleate and eicosenoate were negatively correlated with C-terminal telopeptide of type 1 collagen (CTX-1, a bone resorption marker), while arachidonate was negative correlated with osteocalcin (OCN, a bone formation marker) (p < 0.05). A significant correlation was also found between eicosenoate and NOS (p < 0.05). Profound bone marrow fatty acids changes have taken place in the early stage of post-menopausal osteoporosis. They may affect bone formation though affecting the differentiation and function of osteoclasts or osteoblasts, respectively. The NOS/NO system may mediate the influence of eicosenoate on bone formation. Full article

Nurses are frontline care providers whose health is vital to providing good quality of care to patients. The purpose of this study was to develop an exercise program for high-risk metabolic syndrome nurses based on the transtheoretical model. The transtheoretical model was used in this study due to its popular use in exercise behavior change and it can clearly identify the stage of exercise so as to plan an effective program to promote health. This was a quasi-experimental pilot study with a total of 40 participants who met the inclusion criteria. Exercise programs were developed for three groups distinguished by their commitment to exercising for health. Sixteen (40%) nurses moved one step forward, six (15%) nurses moved backward, and eighteen (45%) nurses maintained at the same stage over time (stable sedentary, 40%; stable active, 5%). Bowker’s test of symmetry, χ2 = 14.00 (p < 0.01), revealed that the population exercising increased significantly after the intervention. After the program, the perceived benefits from exercise in the decisional balance significantly increased to 1.53 (t = 2.223, p < 0.05), perceived exercise barriers significantly decreased to 3.10 (t = −3.075, p < 0.05), and self-efficacy significantly increased to 2.90 (t = 3.251, p < 0.01), respectively. Applying the transtheoretical model to health behavior enables significant change. The benefits of applying the transtheoretical model for promoting exercise include increasing perceived exercise benefits and self-efficacy, decreasing perceived exercise barriers, and increasing physical activity levels. Full article

We perform quantitative studies to investigate the effect of high-calorie diet on Drosophila oogenesis. We use the central composite design (CCD) method to obtain quadratic regression models of body fat and fertility as a function of the concentrations of protein and sucrose, two major macronutrients in Drosophila diet, and treatment duration. Our results reveal complex interactions between sucrose and protein in impacting body fat and fertility when they are considered as an integrated physiological response. We verify the utility of our quantitative modeling approach by experimentally confirming the physiological responses—including increased body fat, reduced fertility, and ovarian insulin insensitivity—expected of a treatment condition identified by our modeling method. Under this treatment condition, we uncover a Drosophila oogenesis phenotype that exhibits an accumulation of immature oocytes and a halt in the production of mature oocytes, a phenotype that bears resemblance to key aspects of the human condition of polycystic ovary syndrome (PCOS). Our analysis of the dynamic progression of different aspects of diet-induced pathophysiology also suggests an order of the onset timing for obesity, ovarian dysfunction, and insulin resistance. Thus, our study documents the utility of quantitative modeling approaches toward understanding the biology of Drosophila female reproduction, in relation to diet-induced obesity and type II diabetes, serving as a potential disease model for human ovarian dysfunction. Full article

Background. Snoring is the cardinal symptom of obstructive sleep apnea (OSA). The acoustic features of snoring sounds include intra-snore (including snoring index [SI]) and inter-snore features. However, the correlation between snoring sounds and the severity of OSA according to the apnea–hypopnea index (AHI) is still unclear. We aimed to use the snoring index (SI) and the Epworth Sleepiness Scale (ESS) to predict OSA and its severity according to the AHI among middle-aged participants referred for polysomnography (PSG). Methods. In total, 50 participants (mean age, 47.5 ± 12.6 years; BMI: 29.2 ± 5.6 kg/m²) who reported snoring and were referred for a diagnosis of OSA and who underwent a whole night of PSG were recruited. Results. The mean AHI was 30.2 ± 27.2, and the mean SI was 87.9 ± 56.3 events/hour. Overall, 11 participants had daytime sleepiness (ESS > 10). The correlation between SI and AHI (r = 0.33, p = 0.021) was significant. Univariate linear regression analysis showed that male gender, body mass index, neck circumference, ESS, and SI were associated with AHI. SI (β = 0.18, p = 0.004) and neck circumference (β = 2.40, p < 0.001) remained significantly associated with AHI by the multivariate linear regression model. Conclusion. The total number of snores per hour of sleep and neck circumference were positively associated with OSA among adults referred for PSG. Full article

Irritable Bowel Syndrome (IBS) is usually a lifelong state that disturbs the digestive system. IBS has been linked to low-grade inflammation and the release of inflammatory mediators into the bloodstream. This could be associated with the degree of obesity presented by patients with IBS. Reports imply that IBS is more frequent in obese patients than in the overall population, with a prevalence of up to 31%. Here, we evaluated the serum levels of immunological and inflammation molecules and their correlation with Body Mass Index in IBS patients and the healthy control (HC). Seventy-nine serum samples of the IBS patients and thirty-five of the HC group were analyzed to determine the levels of each molecule and compare them with their BMI. Serum levels of C3 and C4 were significantly increased in IBS patients. C3 and C4 levels were higher in IBS-M and IBS-D subtypes compared with the HC group. When patients were grouped by BMI, a positive correlation between serum C3 (r = 0.49, p < 0.0001) and CRP (r = 0.40, p < 0.001) levels was found. Our results show, for the first time, a correlation between immunological molecules and BMI in IBS patients, suggesting that the inflammatory nature of obesity could contribute to the development of the symptoms in IBS through the stimulation and release of proteins as complement components and CRP. Full article

This study aimed to compare phase angle (PhA) and bioelectrical impedance vector analysis (BIVA) values between adult patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH21OHD) and a control group. A total of 22 patients (15 women, 22.9 ± 3.7 years) were compared with 17 controls (11 women, 27.0 ± 2.5 years). Body composition was determined by dual-energy X-ray absorptiometry. Bioelectrical impedance was used to calculate PhA, and BIVA was performed using specific software. Student’s t-test and analysis of covariance were used to compare groups. Hedges’ G and partial n² were calculated for the effect estimates. Hotelling’s t² test was used to compare the mean impedance vectors between the groups. The Mahalanobis test was used to determine the distance between confidence ellipses. Patients with CAH21OHD had a higher fat mass percentage than that of the control group (both sexes). There was no significant difference in PhA values between groups (CAH21OHD vs. control) in females (6.9° vs. 6.3°, p = 0.092) and males (8.2° vs. 8.1°, p = 0.849), after adjusting for covariates (age and height). BIVA analysis showed a significant difference in the mean impedance vectors between the female groups (T² = 15.9, D = 1.58, p = 0.003) owing to the higher reactance/height (Δ = 8.5; p < 0.001) of the patients. The PhA did not significantly differ between the groups. Female patients had significantly higher reactance values. However, further studies are needed to determine the usefulness of bioimpedance parameters in evaluating the hydration status and cellular integrity of patients with CAH21OHD. Full article

Background: Resistin is a proinflammatory adipokine involved in metabolic disorders. Its interplay with hypertriglyceridemia remains to be elucidated. We aimed to evaluate the relationship between resistin (−420C/G) single nucleotide variant (SNV) and metabolic parameters and preference for fried food consumption in hypertriglyceridemia. Methods: The study enrolled 179 hypertriglyceridemic (HTG) and 182 normotriglyceridemic (NTG) patients. Anthropometric measurements, serum resistin, insulin and fasting glucose concentration, a homeostatic model assessment—insulin resistance (HOMA-IR), triglycerides (TG), cholesterol concentration, and fried food taste preference (FP) or other cooking methods preference (OP) were assessed in the study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: HTG and NTG groups did not differ significantly in serum resistin concentration; HTG individuals demonstrated significantly increased serum levels of TG, glucose, total cholesterol (TCH), and HOMA-IR and decreased HDL cholesterol. Resistin, insulin, glucose, HOMA-IR, and cholesterol fractions were similar among particular resistin genotypes in HTG, NTG, FP, or OP groups. TG and TCH concentrations differ significantly among CG and CC genotypes in the FP group. Considering the FP group, GG and CG genotypes appeared more frequently in hyperlipidemic (OR 2.6 95% CI; 1.16–5.82; p = 0.01; significant after Bonferroni correction) than in NTG patients. Multivariable logistic regression models showed that the G allele and CG genotype of SNV (−420C/G), adjusted for selected confounders such as fried food preference, increased the odds of hypertriglyceridemia about twofold. Conclusions: Allele G and CG genotype of resistin SNV (−420C/G) are linked with the preference for fried food taste in hypertriglyceridemic patients. Full article

Objective: This study aims to summarize the characteristics of diagnosed pneumoconiosis and pneumoconiosis death in the Hubei Province of China, between the years 1949 and 2019, and provide clues for the scientific prevention of pneumoconiosis. Methods: We recruited 23,069 pneumoconiosis cases in Hubei Province, China, from 1949 to 2019. Basic information and occupational surveillance information were obtained from the Hubei Occupational Diseases and Health Risk Factors Information Surveillance System. Results: The annually diagnosed pneumoconiosis cases showed an overall increasing trend from 1949 to 2019 in Hubei Province. The major types of pneumoconiosis were coal workers’ pneumoconiosis (CWP, 49.91%) and silicosis (43.39%). Pneumoconiosis cases were mainly engaged in mining (75.32%) and manufacturing (12.72%), and were distributed in Huangshi (35.48%), Yichang (16.16%), and Jingzhou (7.97%). CWP (47.50%) and silicosis (44.65%) accounted for most of the deaths. Conclusions: The number of pneumoconiosis cases and deaths in Hubei increased in the period of 1949 to 2019. Silicosis and CWP contributed to the predominant types of pneumoconiosis. Prevention and control measures should continue to be taken to reduce the morbidity and mortality of pneumoconiosis. Full article

(1) Background: Obesity is a global epidemic issue that has increased greatly in recent decades. Although interventions such as nutritional approaches and the practice of physical exercise are potential therapies to combat obesity, in some cases they are not sufficient. Therefore, the development of new pharmacological treatments is necessary. Combining these therapies with non-pharmacological alternatives could be an interesting strategy for treating obesity. Considered a pharmacological treatment for overactive bladder (OAB), mirabegron is also categorized as a β(3)-adrenoceptor agonist, and is used in recommended doses of 25 mg and 50 mg. Animal models have shown that the administration of 0.8 mg/kg of mirabegron leads to elevated activation of brown adipose tissue (BAT) and white adipose tissue (WAT) browning. (2) Results: Findings suggest that the pharmacological application of mirabegron has numerous beneficial effects in lipid metabolism, suggesting a potential action against obesity. In this context, physical exercise and mirabegron stimulate browning activation using different mechanisms. (3) Conclusions: According to the results of the studies presented in this review, mirabegron may be a promising pharmacological treatment for obesity due to its significant effects on estimated energy expenditure (EER) through thermogenesis elevation, BAT activation, and WAT browning seen in dosages up to 100 mg. In addition, the administration of mirabegron combined with physical exercise may be a potential alternative for increasing the body’s energy expenditure, with actions in distinct signaling pathways. Thus, physical exercise combined with mirabegron can alleviate some adverse side effects encountered with the use of the medication. Finally, although there have been advances in knowledge, more studies are needed to understand the combined effects of using mirabegron and physical exercise. Full article

(1) Background: This work aims to investigate the metabolomic changes in PIGinH11 pigs and investigate differential compounds as potential therapeutic targets for metabolic diseases. (2) Methods: PIGinH11 pigs were established with a CRISPR/Cas9 system. PNPLA3^I148M, hIAPP, and GIPR^dn were knocked in the H11 locus of the pig genome. The differential metabolites between and within groups were compared at baseline and two months after high-fat-high-sucrose diet induction. (3) Results: 72.02% of the 815 detected metabolites were affected by the transgenic effect. Significantly increased metabolites included isoleucine, tyrosine, methionine, oxoglutaric acid, acylcarnitine, glucose, sphinganines, ceramides, and phosphatidylserines, while fatty acids and conjugates, phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins were decreased. Lower expression of GPAT3 and higher expression of PNPLA3^I148M decreased the synthesis of diacylglycerol and phosphatidylcholines. Accumulated ceramides that block Akt signaling and decrease hyocholic acid and lysophosphatidylcholines might be the main reason for increased blood glucose in PIGinH11 pigs, which was consistent with metabolomic changes in patients. (4) Conclusions: Through serum metabolomics and lipidomics studies, significant changes in obesity and diabetes-related biomarkers were detected in PIGinH11 pigs. Excessive fatty acids β-oxidation interfered with glucose and amino acids catabolism and reduced phosphatidylcholines. Decreased hyocholic acid, lysophosphatidylcholine, and increased ceramides exacerbated insulin resistance and elevated blood glucose. Phosphatidylserines were also increased, which might promote chronic inflammation by activating macrophages. Full article

Cardiac function is closely related to heart metabolism. Heart failure patients undergoing LVAD support have shown varying degrees of remodeling of both cardiac function and morphology. However, the metabolic changes in patients with different outcomes are unclear. This study aimed to identify metabolic differences and evaluate metabolomics-based biomarkers in patients with non-improved/improved cardiac function after LVAD support. Sixteen patients were enrolled in this study. Plasma samples were analyzed by using untargeted metabolomic approaches. Multivariate statistical analysis and a Mann–Whitney U-test was performed to clarify the separation in metabolites and to identify changes in plasma metabolites between the two groups, respectively. The efficacy of candidate biomarkers was tested by the area under the curve receiver operating characteristic curve. Using the Metabolomics Standards Initiative level 2, a total of 1542 and 619 metabolites were detected in the positive and negative ion modes, respectively. Enrichment analysis showed that metabolites in improved cardiac function patients were mainly involved in carbohydrate metabolism and amino acid metabolism. Metabolites from non-improved cardiac function patients were mainly involved in hormone metabolism. Furthermore, we found tris(hydroxymethyl)aminomethane and 5-guanidino-3-methyl-2-oxopentanoic acid could serve as biomarkers to predict whether a patient’s cardiac function would improve after LVAD support. Full article

Our skin is an organ with the largest contact area between the human body and the external environment. Skin aging is affected directly by both endogenous factors and exogenous factors (e.g., UV exposure). Skin saccharification, a non-enzymatic reaction between proteins, e.g., dermal collagen and naturally occurring reducing sugars, is one of the basic root causes of endogenous skin aging. During the reaction, a series of complicated glycation products produced at different reaction stages and pathways are usually collectively referred to as advanced glycation end products (AGEs). AGEs cause cellular dysfunction through the modification of intracellular molecules and accumulate in tissues with aging. AGEs are also associated with a variety of age-related diseases, such as diabetes, cardiovascular disease, renal failure (uremia), and Alzheimer’s disease. AGEs accumulate in the skin with age and are amplified through exogenous factors, e.g., ultraviolet radiation, resulting in wrinkles, loss of elasticity, dull yellowing, and other skin problems. This article focuses on the damage mechanism of glucose and its glycation products on the skin by summarizing the biochemical characteristics, compositions, as well as processes of the production and elimination of AGEs. One of the important parts of this article would be to summarize the current AGEs inhibitors to gain insight into the anti-glycation mechanism of the skin and the development of promising natural products with anti-glycation effects. Full article

Increases in longevity and obesity have led to a higher prevalence of Metabolic Syndrome (MetS) and several chronic conditions, such as hypertension. The prevalence of MetS and hypertension increases with advancing age and their detrimental effects on health can be attenuated by physical activity. Combined aerobic and resistance exercise training (CT) is recommended to maintain good health in older adults and is known to generate important metabolic adaptations. In this study we performed a metabolomics analysis, based on Hydrogen Nuclear Magnetic Resonance (1H NMR), to investigate the kinetics of changes in metabolism in non-physically active older women with MetS in response to 16 weeks of CT. A subset of women with MetS were selected from a larger randomized trial (that included men and women without MetS), with 12 participants on CT and 13 from the Control Group (CG). CT comprised walking/running at 63% of VO₂max, three times/week, and resistance training (RT), consisting of 15 repetitions of seven exercises at moderate intensity, twice/week. Serum metabolomic profile was analysed at baseline (0W), 4 (4W), 8 (8W), 12 (12W) and 16 weeks (16W) for CT or CG. Cardiorespiratory fitness, RT load, blood pressure, body composition, lipid and glycaemic profile were also assessed. After 16 weeks CT increased cardiorespiratory fitness (13.1%, p < 0.05) and RT load (from 48% in the lat pulldown to 160% in the leg press, p < 0.05), but there were no changes in MetS parameters, such as body composition (Body Mass, Body Mass Index (BMI), body fat percentage and waist circumference), blood pressure, lipid and glycaemic profile. However, we identified potential higher substrate to the tricarboxylic acid cycle (increase in 2-Oxobutyrate from 0W (0.0029 ± 0.0009) to 4W (0.0038 ± 0.0011) and 8W (0.0041 ± 0.0015), p < 0.05), followed by alterations (different from 0W, p < 0.05) in the production of ketone bodies (3-Hydroxybutyrate, 0W (0.0717 ± 0.0377) to 16W (0.0397 ± 0.0331), and Acetoacetate, 0W (0.0441 ± 0.0240) to 16W (0.0239 ± 0.0141)), which together might explain the known improvement in fatty acid oxidation with exercise. There was also a late increase in ornithine at 16W of CT. Further studies are needed to investigate the association between these metabolic pathways and clinical outcomes in this population. Full article

The present high mortality of lung cancer in China stems mainly from the lack of feasible, non-invasive and early disease detection biomarkers. Serum metabolomics profiling to reveal metabolic alterations could expedite the disease detection process and suggest those patients who are harboring disease. Using a nested case-control design, we applied ultra-high-performance liquid chromatography/mass spectrometry (LC-MS)-based serum metabolomics to reveal the metabolomic alterations and to indicate the presence of non-small cell lung cancer (NSCLC) using serum samples collected prior to disease diagnoses. The studied serum samples were collected from 41 patients before a NSCLC diagnosis (within 3.0 y) and 38 matched the cancer-free controls from the prospective Shanghai Suburban Adult Cohort. The NSCLC patients markedly presented cellular metabolism alterations in serum samples collected prior to their disease diagnoses compared with the cancer-free controls. In total, we identified 18 significantly expressed metabolites whose relative abundance showed either an upward or a downward trend, with most of them being lipid and lipid-like molecules, organic acids, and nitrogen compounds. Choline metabolism in cancer, sphingolipid, and glycerophospholipid metabolism emerged as the significant metabolic disturbance of NSCLC. The metabolites involved in these biological processes may be the distinctive features associated with NSCLC prior to a diagnosis. Full article

This study aimed to examine lifestyle factors associated with the change in glucose categories among individuals without diabetes. We analyzed cohort data of medical check-ups at baseline between April 2008 and December 2012. The primary and secondary outcomes were the change in glucose categories from normoglycemia (glycated hemoglobin (HbA1c) < 5.7% and fasting plasma glucose (FPG) < 5.6 mmol/L) to prediabetes (HbA1c 5.7–6.4% or FPG 5.6–6.9 mmol/L) and from prediabetes to normoglycemia. During a mean follow-up of 2.4 years, 7083 of 57,018 individuals with normoglycemia developed prediabetes, whereas 4629 of 9926 individuals with prediabetes returned to normoglycemia. Factors associated with progression to prediabetes were baseline BMI (hazard ratio [95% confidence interval]: 1.08 [1.07–1.09]), change in BMI during follow-up (1.05 [1.03–1.07]), late dinner/snacking (1.16 [1.10–1.22]), skipping breakfast (1.12 [1.06–1.18]), and heavy alcohol consumption (1.33 [1.24–1.42]). Factors associated with return to normoglycemia from prediabetes were baseline BMI (0.94 [0.93–0.95]) and change in BMI during follow-up (0.95 [0.93–0.97]). In conclusion, poor eating behaviors, such as skipping breakfast, late dinner/snacking, and heavy alcohol consumption, were associated with the progression from normoglycemia to prediabetes. Full article

This study investigated the effects of metabolic syndrome on the estimated glomerular filtration rate in middle-aged participants with diabetes to provide basic data to enable the development of education programs for middle-aged people to prevent diabetic kidney disease. This cross-sectional descriptive study analyzed data obtained in the 2nd year of the 8th Korea National Health and Nutrition Examination Survey in 2020 and enrolled 279 participants aged 40–65 years who were diagnosed with diabetes. Multilevel stratified cluster sampling was used to improve the representativeness of the samples and the accuracy of parameter estimation. The risk factors of metabolic syndrome and the risk of elevated eGFR were analyzed using regression analysis and the correlation between the variables was determined using Pearson’s correlation analysis. Middle-aged participants with diabetes whose eGFR was <90 showed a significant difference in their risk for metabolic syndrome based on sex, age, disease duration, and total cholesterol concentrations. Systolic blood pressure and waist circumference in men, and waist circumference and HDL cholesterol level in women were identified as risk factors that contribute to the increasing prevalence of metabolic syndrome. Full article

The single nucleotide polymorphism (SNP) rs4148727 in ABCB1 (encoding p-glycoprotein) is associated with lipid levels; however, its association with type 2 diabetes (T2DM) and its the genetic correlation with lipid profiles and T2DM are unclear. We included 2300 participants from 593 families. A generalized estimating equations (GEE) model and Cox regression models were used to estimate the SNP’s effects on T2DM and lipid profiles. The participation of the SNP in T2DM pathogenesis through lipid-associated pathways was tested using mediation analysis. The G allele of the SNP was related to a 32% (6–64%, p = 0.015) increase in T2DM risk. It was also associated with a 10% (1–20%, p = 0.029), 17% (3–32%, p = 0.015), and 4% (1–7%, p = 0.015) increment in total cholesterol (TC), triglyceride (TG), and apolipoprotein A (Apo-A) concentrations, respectively. According to the mediation analysis, only TG (6.9%) and Apo-B (4.0%) had slight but significant mediation effects on the total impact of the SNP on T2DM. The pleiotropic effects of the ABCB1 variant on T2DM and lipids likely act via different pathways. The biological mechanisms should be verified in a future study. Full article

Metabolic diseases caused by gene and unhealthy living habits are increasing, which seriously threaten the life of people worldwide. Moreover, the microbiome has been shown to play an active role in the prevention and treatment of metabolic diseases. However, reliable evidence on renalase gene (Rnls), as a common gene related to metabolic diseases, is still lacking with regard to the influence on the microbiome. Hence, we investigated the effect of a normal diet (ND) and a high-fat diet (HFD) on the gut microbiota of Rnls knockout (Rnls^−/−) and wild-type (Rnls^+/+) mice. At the end of the 8-week experiment, DNA samples were extracted from fresh feces, and the composition of microbiota was profiled. The species in Rnls^+/+-ND group were Bifidobacterium pseudolongum and Lactobacillus reuteri. Conversely, the species in Rnls^−/−-ND group belonged to the genera Lactobacillus and Turicibacter. The HFD changed the ratio of Firmicutes/Bacteroidetes; while the bacteria in the Rnls^+/+-HFD and Rnls^−/−-HFD groups were different. Overall, this study not only revealed the composition of microbiota in Rnls^−/− mice, but also indicated that Rnls and the bacteria related to Rnls may be new candidates in the prevention and diagnosis of metabolic diseases at an early stage. Full article

Metabolic syndrome (MetS) is a group of several metabolic conditions predisposing to chronic diseases. Individuals diagnosed with MetS are physiologically heterogeneous, with significant sex-specific differences. Therefore, we aimed to investigate the potential sex-specific serum modifications of amino acids and acylcarnitines (ACs) and their relationship with MetS in the Mexican population. This study included 602 participants from the Health Workers Cohort Study. Forty serum metabolites were analyzed using a targeted metabolomics approach. Multivariate regression models were used to test associations of clinical and biochemical parameters with metabolomic profiles. Our findings showed a serum amino acid signature (citrulline and glycine) and medium-chain ACs (AC14:1, AC10, and AC18:10H) associated with MetS. Glycine and AC10 were specific metabolites representative of discrimination according to sex-dependent MetS. In addition, we found that glycine and short-chain ACs (AC2, AC3, and AC8:1) are associated with age-dependent MetS. We also reported a significant correlation between body fat and metabolites associated with sex-age-dependent MetS. In conclusion, the metabolic profile varies by MetS status, and these differences are sex-age-dependent in the Mexican population. Full article

Iodine is a mineral nutrient essential for the regulation of a variety of key physiological functions including metabolism and brain development and function in children and adults. As such, iodine intake and status within populations is an area of concern and research focus. This paper will review recently published studies that focus on the re-emerging issue of iodine deficiency as a global concern and declining intake among populations in developed countries. Historically, the implementation of salt-iodization programs worldwide has reduced the incidence of iodine deficiency, but 30% of the world’s population is still at risk. Iodine nutrition is a growing issue within industrialized countries including the U.S. as a result of declining iodine intake, in part due to changing dietary patterns and food manufacturing practices. Few countries mandate universal salt iodization policies, and differing agriculture and industry practices and regulations among countries have resulted in inconsistencies in supplementation practices. In the U.S., in spite of salt-iodization policies, mild-to-moderate iodine deficiency is common and appears to be increasing. European countries with the highest incidence of deficiency lack iodization programs. Monitoring the iodine status of at-risk populations and, when appropriate, public health initiatives, appear to be warranted. Full article

(1) Background: Obesity has become an important public health problem worldwide, and its characterization as a chronic disease reflects the impact of a complex and multifactorial condition. The treatment for obesity is based on lifestyle interventions that induce a negative energy balance. However, adherence to a lifestyle intervention is a challenge for many overweight and obese people. Thus, pharmacotherapy in the management of obesity is used to increase patient adherence to lifestyle changes and overcome the biological adaptations that occur with weight loss. Among these drugs, liraglutide stands out. Liraglutide is an analog of human glucagon-like peptide-1 (GLP-1), a hormone that regulates glucose-dependent insulin secretion, and glucagon release. (2) Results: Liraglutide appears to be effective in weight reduction and glycemic control in diabetic and obese patients, and combination of liraglutide and exercise can also bring benefits in weight loss. Furthermore, the combination of liraglutide and physical exercise can prevent adverse effects observed in the administration of liraglutide. (3) Conclusions: liraglutide seems to contribute to cardiometabolic improvement in obese individuals with or without diabetes, and the combination of liraglutide and physical exercise can prevent adverse effects observed in the administration of liraglutide. Full article

(1) Background: The association between metabolic obesity phenotypes and incident lung cancer (LC) remains unclear. (2) Methods: Based on the combination of baseline BMI categories and metabolic health status, participants were categorized into eight groups: metabolically healthy underweight (MHUW), metabolically unhealthy underweight (MUUW), metabolically healthy normal (MHN), metabolically unhealthy normal (MUN), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). The Cox proportional hazards model and Mendelian randomization (MR) were applied to assess the association between metabolic obesity phenotypes with LC risk. (3) Results: During a median follow-up of 9.1 years, 3654 incident LC patients were confirmed among 450,482 individuals. Compared with participants with MHN, those with MUUW had higher rates of incident LC (hazard ratio (HR) = 3.24, 95% confidence interval (CI) = 1.33–7.87, p = 0.009). MHO and MHOW individuals had a 24% and 18% lower risk of developing LC, respectively (MHO: HR = 0.76, 95% CI = 0.61–0.95, p = 0.02; MHO: HR = 0.82, 95% CI = 0.70–0.96, p = 0.02). No genetic association of metabolic obesity phenotypes and LC risk was observed in MR analysis. (4) Conclusions: In this prospective cohort study, individuals with MHOW and MHO phenotypes were at a lower risk and MUUW were at a higher risk of LC. However, MR failed to reveal any evidence that metabolic obesity phenotypes would be associated with a higher risk of LC. Full article

Worldwide, obesity rates have doubled since the 1980s and in the USA alone, almost 40% of adults are obese, which is closely associated with a myriad of metabolic diseases such as type 2 diabetes and arteriosclerosis. Obesity is derived from an imbalance between energy intake and consumption, therefore balancing energy homeostasis is an attractive target for metabolic diseases. One therapeutic approach consists of increasing the number of brown-like adipocytes in the white adipose tissue (WAT). Whereas WAT stores excess energy, brown adipose tissue (BAT) can dissipate this energy overload in the form of heat, increasing energy expenditure and thus inhibiting metabolic diseases. To facilitate BAT production a high-throughput screening approach was developed on previously known drugs using human Simpson–Golabi–Behmel Syndrome (SGBS) preadipocytes. The screening allowed us to discover that zafirlukast, an FDA-approved small molecule drug commonly used to treat asthma, was able to differentiate adipocyte precursors and white-biased adipocytes into functional brown adipocytes. However, zafirlukast is toxic to human cells at higher dosages. Drug-Initiated Activity Metabolomics (DIAM) was used to investigate zafirlukast as a BAT inducer, and the endogenous metabolite myristoylglycine was then discovered to mimic the browning properties of zafirlukast without impacting cell viability. Myristoylglycine was found to be bio-synthesized upon zafirlukast treatment and was unique in inducing brown adipocyte differentiation, raising the possibility of using endogenous metabolites and bypassing the exogenous drugs to potentially alleviate disease, in this case, obesity and other related metabolic diseases. Full article

Evidence on the association between systolic blood pressure (SBP) trajectories and arterial stiffness progression is scarce. The current study aimed to identify the association between SBP trajectories and the progression of arterial stiffness over time in Chinese adults. This study included 30,384 adult participants. Latent mixture modeling was used to identify the SBP trajectory patterns from 2006 to 2010. The brachial–ankle pulse wave velocity (baPWV) was used to measure arterial stiffness. The associations between SBP trajectories and the progression of arterial stiffness were explored using multiple linear regression models. We identified five distinct SBP trajectories and took the low-stable group as the reference. In the cross-sectional analysis, the four SBP trajectories were significantly associated with higher baPWV levels (p < 0.001) compared with the reference. In the longitudinal analysis, after adjusting for covariates and the baseline baPWV, the SBP trajectories were significantly associated with the progression of the baPWV, with corresponding β (95% CI) values of 23.3 (17.2–29.5) cm/s per year for the moderate-stable group, 44.8 (36.6–52.9) cm/s per year for the moderate-increasing group, 54.6 (42.2–67.0) cm/s per year for the elevated-decreasing group, and 66.8 (54.7–79.0) cm/s per year for the elevated-stable group. Similar significant results were also observed in the non-hypertensive population. In conclusion, SBP trajectories were related to the baseline baPWV and the progression of the baPWV. Blood pressure control may be considered a therapeutic target to further reduce the risk of arterial stiffness. Full article

Background: Little is known about sex differences in the risk of type 2 diabetes (DM2) development related to body fat depot. The main aim of this study was to assess sex-specific differences in the prevalence of diabetes in the relation to body mass, body mass index (BMI), waist circumference (WC), and calculated body fat percentage (BF), adjusted by physical activity, in younger and older hypertensive adults. Subjects/Methods: The survey enrolled 12,289 adult hypertensive outpatients with body weight, height, and WC reported by their physicians across Poland. Prevalence of diabetes was plotted against body mass, BMI, WC, and calculated BF and adjusted by the self-reported level of physical activity. Results: In our cohort, younger women (<60 years) with BMI < 25.0 kg/m² had lower adjusted prevalence of diabetes than corresponding men (3.4% vs. 6.5%), while among older (≥60 years) with BMI < 25.0 kg/m², the prevalence of diabetes was greater in women than in men (19.4% vs. 11.2%). A 25% probability of diabetes was observed for younger women with lower BMI than younger men (32.1 kg/m² and 35.3 kg/m², respectively) and WC (100.7 cm and 116.1 cm, respectively) but greater BF (45.5% and 38.9%, respectively). The corresponding differences in BMI and WC in older ones were much smaller (27.6 kg/m² and 27.2 kg/m², respectively; 83.7 cm and 85.6 cm, respectively), but not for BF (40.7% and 30.1%, respectively). A doubling of diabetes probability (from 25% to 50%), adjusted by physical activity, was attributable to the lower increase in BMI and WC and BF in women than in men (6.3 vs. 9.8 kg/m², 25.0 vs. 36.1 cm, and 6.5 vs. 10.8%, for younger, and 8.1 vs. 11.3 kg/m², 26.2 vs. 73.2 cm and 8.8 vs. 13.3%, for older). Conclusions: This study shows a lower probability of diabetes in younger women than younger men with normal weight BMI ranges, adjusted to physical activity. This probability is greater for hypertensive women, regardless of age, due to the increase in BMI/WC and BF values adjusted for physical activity. Full article

Background. SARS-CoV-2 infection was analyzed according to previous metabolic status and its association with mortality and post-acute COVID-19. Methods. A population-based observational retrospective study was conducted on a cohort of 110,726 patients aged 12 years or more who were diagnosed with COVID-19 infection between June 1st, 2021, and 28 February 2022 on the island of Gran Canaria, Spain. Results. In the 347 patients who died, the combination of advanced age, male sex, cancer, immunosuppressive therapy, coronary heart disease, elevated total cholesterol and reduced high-density lipoprotein cholesterol (HDL-C) was strongly predictive of mortality (p < 0.05). In the 555 patients who developed post-acute COVID-19, the persistence of symptoms was most frequent in women, older subjects and patients with obstructive sleep apnea syndrome, asthma, elevated fasting glucose levels or elevated total cholesterol (p < 0.05). A complete vaccination schedule was associated with lower mortality (incidence rate ratio (IRR) 0.5, 95%CI 0.39–0.64; p < 0.05) and post-acute COVID-19 (IRR 0.37, 95%CI 0.31–0.44; p < 0.05). Conclusions. Elevated HDL-C and elevated total cholesterol were significantly associated with COVID-19 mortality. Elevated fasting glucose levels and elevated total cholesterol were risk factors for the development of post-acute COVID-19. Full article

Endurance training induces several adaptations in substrate metabolism, especially in relation to glycogen conservation. The study aimed to investigate differences in the metabolism of lipids, lipid-like substances, and amino acids between highly trained and untrained subjects using targeted metabolomics. Depending on their maximum relative oxygen uptake (VO_2max), subjects were categorized as either endurance-trained (ET) or untrained (UT). Resting blood was taken and plasma isolated. It was screened for changes of 345 metabolites, including amino acids and biogenic amines, acylcarnitines, glycerophosphocholines (GPCs), sphingolipids, hexoses, bile acids, and polyunsaturated fatty acids (PUFAs) by using liquid chromatography coupled to tandem mass spectrometry. Acylcarnitine (C14:1, down in ET) and five GPCs (lysoPC a C18:2, up in ET; PC aa C42:0, up in ET; PC ae C38:2, up in ET; PC aa C38:5, down in ET; lysoPC a C26:0, down in ET) were differently regulated in ET compared to UT. TCDCA was down-regulated in athletes, while for three ratios of bile acids CA/CDCA, CA/(GCA+TCA), and DCA/(GDCA+TDCA) an up-regulation was found. TXB2 and 5,6-EET were down-regulated in the ET group and 18S-HEPE, a PUFA, showed higher levels in 18S-HEPE in endurance-trained subjects. For PC ae C38:2, TCDCA, and the ratio of cholic acid to chenodeoxycholic acid, an association with VO_2max was found. Numerous phospholipids, acylcarnitines, glycerophosphocholines, bile acids, and PUFAs are present in varying concentrations at rest in ET. These results might represent an adaptation of lipid metabolism and account for the lowered cardiovascular risk profile of endurance athletes. Full article

The aim of this study was to evaluate the effects of being overweight on the ability to conceive, fertilization rate, and in vivo development of embryos in regularly cycling, spontaneously ovulating, and naturally mated female mice. The study was based on statistical analysis of data collected during 14 experiments with identical design, performed on 319 control and 327 obese mice, developed in an intergenerational model of obesity induction which eliminates the impact of aging and high-fat feeding. Six-week-old mice with a vaginal sperm plug were slaughtered on embryonic days 2, 3, or 4, and the flushed contents of the oviducts and uteri were assessed by stereomicroscopy. The results showed no association between being overweight and the proportion of ovulating or fertilized females. On the other hand, a strong association was found between being overweight and ovulation yield. On embryonic day 2, significantly higher numbers of eggs were recovered from the oviducts of fertilized obese mice. Maternal overweight status was also associated with higher developmental capacities of preimplantation embryos. In conclusion, contrary to studies based on the high-fat-diet model, in female mice fed regular chow, being overweight was associated with an increased ovulation quota and higher developmental rate of fertilized oocytes. Being overweight did not impact ability to conceive. On the other hand, as documented in our previous studies, the quality of oocytes and blastocysts recovered from overweight mice developed in an intergenerational model of obesity was low. Full article

It is unclear how the dietary patterns reflecting C-reactive protein (CRP) affect metabolic syndrome (MetS) in the Chinese population. To examine the effect of the dietary pattern reflecting CRP with MetS, a cross-sectional study was based on the health checkup data from the Beijing MJ Health Screening Centers between 2008 and 2018. The CRP-related dietary pattern was derived from 17 food groups using reduced-rank regression. Participants were divided into five groups according to the quintiles of dietary pattern score. Multivariate logistic regression was then applied to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for the quintiles of diet pattern score related to MetS and its four components. Of the 90,130 participants included in this study, 11,209 had MetS. A CRP-related dietary pattern was derived, characterized by a higher consumption of staple food, fresh meat, processed products, and sugar-sweetened beverages but a lower intake of honey and jam, fruits, and dairy products. Compared with participants in the lowest quintile (Q1), participants in the higher quintiles were associated with increased risks of MetS in a dose–response manner after adjustment for potential confounders (p for linear trend < 0.001), the ORs for Q2 to Q5 were 1.10 (95% CI: 1.02–1.19), 1.14 (95% CI: 1.05–1.22), 1.23 (95% CI: 1.15–1.33), and 1.49 (95% CI: 1.38–1.61), respectively. Moreover, the effects were stronger among individuals aged 50 years or older. A CRP-related dietary pattern was associated with the risk of MetS. It provides new insights that dietary intervention to achieve a lower inflammatory level could potentially prevent MetS. Full article