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Metabolites, Volume 12, Issue 12 (December 2022) – 141 articles

Cover Story (view full-size image): SLCO1B1 protein transports statins into the liver. SLCO1B1 rs4149056-C impairs simvastatin transport into to the liver and consequently increases its concentration in plasma. We did not find an association of rs4149056-C with the risk of T2D, suggesting that simvastatin increases the risk of T2D. We also investigated the metabolite profile of rs4149056-C in participants on simvastatin treatment and without any statin treatment. Simvastatin treatment decreased concentrations of dicarboxylic acids and increased the turnover of cholesterol into bile acids, which decreases steroidogenesis. Our findings suggest that simvastatin lowers LDL cholesterol through multiple pathways, including dicarboxylic acids, bile acids, steroids, and glycerophospholipids. View this paper
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20 pages, 6101 KiB  
Article
Comparative Investigation of Raw and Processed Radix Polygoni Multiflori on the Treatment of Vascular Dementia by Liquid Chromatograph−Mass Spectrometry Based Metabolomic Approach
by Fengye Wu, Yunlin Li, Wenya Liu, Ran Xiao, Benxing Yao, Mingzhe Gao, Di Xu and Junsong Wang
Metabolites 2022, 12(12), 1297; https://doi.org/10.3390/metabo12121297 - 19 Dec 2022
Cited by 3 | Viewed by 1741
Abstract
Radix Polygoni Multiflori (PM) is a well−known nootropic used in traditional Chinese medicine (TCM). Considering the efficacy and application discrepancy between raw (RPM) and processed PM (PPM), the similarities and differences between them in the treatment of vascular dementia (VaD) is intriguing. In [...] Read more.
Radix Polygoni Multiflori (PM) is a well−known nootropic used in traditional Chinese medicine (TCM). Considering the efficacy and application discrepancy between raw (RPM) and processed PM (PPM), the similarities and differences between them in the treatment of vascular dementia (VaD) is intriguing. In this study, a VaD rat model was constructed by 2−vessel occlusion (2−VO). During 28 days of treatment, plasma was collected on days 7, 14, 21, and 28 after the start of dosing and the metabolic profile was analyzed by HPLC−MS/MS−based metabolomics. The Morris Water Maze Test, hematoxylin–eosin and Nissl staining, and biochemical analysis were used to assess cognitive function, pathogenic alterations and oxidative stress, respectively. RPM and PPM effectivelyreducedthe 2VO−induced cognitive impairment and mitigated histological alterations in hippocampus tissue. The 2−VO model significantly elevated MDA level and decreased SOD activity and GSH level, indicating severe oxidative stress, which could also be attenuated by RPM and PPM treatment. RPM outperformed PPM in decreasing MDA levels while PPM outperformed RPM in increasing GSH levels. Differential metabolites were subjected to Metabolite Set Enrichment Analysis (MSEA) and genes corresponding to proteins having interactions with metabolites were further annotated with Gene Ontology (GO). Both RPM and PPM ameliorated VaD−relevant vitamin B6 metabolism, pentose phosphate pathways, and taurine and hypotaurine metabolism. In addition, the metabolism of cysteine and methionine was regulated only by RPM, and riboflavin metabolism was modulated only by PPM. The results suggested that raw and processed PM had comparable efficacy in the treatment of VaD but also with some mechanistic differenece. Full article
(This article belongs to the Special Issue Metabolomics-Driven Drug Discovery and Evaluation)
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21 pages, 4324 KiB  
Article
Integrated Analysis of Widely Targeted Metabolomics and Transcriptomics Reveals the Effects of Transcription Factor NOR-like1 on Alkaloids, Phenolic Acids, and Flavonoids in Tomato at Different Ripening Stages
by Xinyu Yang, Xiaodan Zhao, Daqi Fu and Ying Zhao
Metabolites 2022, 12(12), 1296; https://doi.org/10.3390/metabo12121296 - 19 Dec 2022
Cited by 8 | Viewed by 1802
Abstract
Tomato is abundant in alkaloids, phenolic acids, and flavonoids; however, the effect of transcription factor NOR-like1 on these metabolites in tomato is unclear. We used a combination of widely targeted metabolomics and transcriptomics to analyze wild-type tomatoes and CR-NOR-like1 tomatoes. A total of [...] Read more.
Tomato is abundant in alkaloids, phenolic acids, and flavonoids; however, the effect of transcription factor NOR-like1 on these metabolites in tomato is unclear. We used a combination of widely targeted metabolomics and transcriptomics to analyze wild-type tomatoes and CR-NOR-like1 tomatoes. A total of 83 alkaloids, 85 phenolic acids, and 96 flavonoids were detected with significant changes. Combined with a KEGG enrichment analysis, we revealed 16 differentially expressed genes (DEGs) in alkaloid-related arginine and proline metabolism, 60 DEGs were identified in the phenolic acid-related phenylpropane biosynthesis, and 30 DEGs were identified in the flavonoid-related biosynthesis pathway. In addition, some highly correlated differential-expression genes with differential metabolites were further identified by correlation analysis. The present research provides a preliminary view of the effects of NOR-like1 transcription factor on alkaloid, phenolic acid, and flavonoid accumulation in tomatoes at different ripening stages based on widely targeted metabolomics and transcriptomics in plants, laying the foundation for extending fruit longevity and shelf life as well as cultivating stress-resistant plants. Full article
(This article belongs to the Special Issue Comprehensive Metabolic Profiling in Fruits)
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18 pages, 854 KiB  
Article
A Targeted and an Untargeted Metabolomics Approach to the Volatile Aroma Profile of Young ‘Maraština’ Wines
by Ana Boban, Urska Vrhovsek, Silvia Carlin, Ana Mucalo and Irena Budić-Leto
Metabolites 2022, 12(12), 1295; https://doi.org/10.3390/metabo12121295 - 19 Dec 2022
Cited by 5 | Viewed by 1935
Abstract
This study investigated the detailed volatile aroma profile of young white wines of Maraština, Vitis Vinifera L., produced by spontaneous fermentation. The wines were produced from 10 vineyards located in two Dalmatian subregions (Northern Dalmatia and Central and Southern Dalmatia). Volatile compounds from [...] Read more.
This study investigated the detailed volatile aroma profile of young white wines of Maraština, Vitis Vinifera L., produced by spontaneous fermentation. The wines were produced from 10 vineyards located in two Dalmatian subregions (Northern Dalmatia and Central and Southern Dalmatia). Volatile compounds from the wine samples were isolated by solid-phase extraction (SPE) and analyzed by an untargeted approach using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC/TOF-MS) and a targeted approach by gas chromatography–tandem mass spectrometry (GC-MS/MS). A comprehensive two-dimensional GC×GC analysis detailed the total volatile metabolites in the wines due to its excellent separation ability. More than 900 compounds were detected after untargeted profiling; 188 of them were identified or tentatively identified. A total of 56 volatile compounds were identified and quantified using GC-MS/MS analysis. The predominant classes in Maraština wines were acids, esters, and alcohols. The key odorants with odor activity values higher than one were β-damascenone, ethyl caprylate, ethyl isovalerate, ethyl 2-methylbutyrate, ethyl caproate, isopentyl acetate, ethyl butyrate, and phenylacetaldehyde. The metabolomics approach can provide a large amount of information and can help to anticipate variation in wines or change winemaking procedures. Full article
(This article belongs to the Special Issue Grape and Wine Metabolome Analysis)
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11 pages, 2411 KiB  
Article
A Preliminary Pilot Study: Metabolomic Analysis of Saliva in Oral Candidiasis
by Takuya Adachi, Norishige Kawanishi, Narumi Ichigaya, Masahiro Sugimoto, Noriyuki Hoshi and Katsuhiko Kimoto
Metabolites 2022, 12(12), 1294; https://doi.org/10.3390/metabo12121294 - 19 Dec 2022
Cited by 1 | Viewed by 1645
Abstract
Early detection of oral candidiasis is essential. However, most currently available methods are time-consuming and useful only for screening patients. Previous studies on the relationship between oral candidiasis and saliva have focused on saliva volume and not on its components. Therefore, to clarify [...] Read more.
Early detection of oral candidiasis is essential. However, most currently available methods are time-consuming and useful only for screening patients. Previous studies on the relationship between oral candidiasis and saliva have focused on saliva volume and not on its components. Therefore, to clarify the effects of oral candidiasis on salivary metabolites, the relationship between salivary components and oral candidiasis was investigated by comparing the salivary metabolites of oral candidiasis patients and those not previously diagnosed with candidiasis. Forty-five participants visiting our university hospital were included and classified into two groups, the Candida group and the control group, based on the Candida detection test results. The unstimulated saliva was collected using the spitting method over 15 min, and the stimulated saliva was collected using the gum-chewing method over 10 min. The saliva volume was measured, and the saliva samples were frozen and analyzed metabolomically. Metabolome analysis revealed 51 metabolites with peak detection rates exceeding 50%. There was no significant difference in age and sex between the Candida and control groups. In the Candida group, five metabolites (tyrosine, choline, phosphoenolpyruvate, histidine, and 6-phosphogluconate) were significantly elevated in the unstimulated, two (octanoic acid and uridine monophosphate(UMP)) were significantly increased, and four (ornithine, butyrate, aminovalerate and aminolevulinate) were significantly decreased in the stimulated saliva. This study suggests the possibility of identifying metabolites specific to patients with oral candidiasis, which could aid prompt diagnosis. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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13 pages, 13306 KiB  
Article
The Metabolomic Profile of the Essential Oil from Zanthoxylum caribaeum (syn. chiloperone) Growing in Guadeloupe FWI using GC × GC-TOFMS
by Lea Farouil, Ryan P. Dias, Gianni Popotte-Julisson, Garrick Bibian, Ahissan Innocent Adou, A. Paulina de la Mata, Muriel Sylvestre, James J. Harynuk and Gerardo Cebrián-Torrejón
Metabolites 2022, 12(12), 1293; https://doi.org/10.3390/metabo12121293 - 19 Dec 2022
Cited by 2 | Viewed by 1672
Abstract
The essential oil (EO) from the leaves of Zanthoxylum caribaeum (syn. Chiloperone) (Rutaceae) was studied previously for its acaricidal, antimicrobial, antioxidant, and insecticidal properties. In prior studies, the most abundant compound class found in leaf oils from Brazil, Costa Rica, and Paraguay [...] Read more.
The essential oil (EO) from the leaves of Zanthoxylum caribaeum (syn. Chiloperone) (Rutaceae) was studied previously for its acaricidal, antimicrobial, antioxidant, and insecticidal properties. In prior studies, the most abundant compound class found in leaf oils from Brazil, Costa Rica, and Paraguay was terpenoids. Herein, essential oil from the leaves of Zanthoxylum caribaeum (prickly yellow, bois chandelle blanc (FWI), peñas Blancas (Costa Rica), and tembetary hu (Paraguay)) growing in Guadeloupe was analyzed with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS), and thirty molecules were identified. A comparison with previously published leaf EO compositions of the same species growing in Brazil, Costa Rica, and Paraguay revealed a number of molecules in common such as β-myrcene, limonene, β-caryophyllene, α-humulene, and spathulenol. Some molecules identified in Zanthoxylum caribaeum from Guadeloupe showed some antimetabolic effects on enzymes; the in-depth study of this plant and its essential oil with regard to metabolic diseases merits further exploration. Full article
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16 pages, 2210 KiB  
Article
Bio-Guided Isolation of New Compounds from Baccharis spp. as Antifungal against Botrytis cinerea
by Ana A. Pinto, Antonio Ruano-González, Abdellah Ezzanad, Cristina Pinedo-Rivilla, Rosario Sánchez-Maestre and Juan Manuel Amaro-Luis
Metabolites 2022, 12(12), 1292; https://doi.org/10.3390/metabo12121292 - 19 Dec 2022
Viewed by 1560
Abstract
Baccharis genus Asteraceae is widely used in traditional treatment against fever, headache, hepatobiliary disorders, skin ulcers, diabetes, and rheumatism, as well as an antispasmodic and diuretic. Its phytochemistry mainly shows the presence of flavonoids and terpenoids such as monoterpenes, sesquiterpenes, diterpenes, and triterpenes. [...] Read more.
Baccharis genus Asteraceae is widely used in traditional treatment against fever, headache, hepatobiliary disorders, skin ulcers, diabetes, and rheumatism, as well as an antispasmodic and diuretic. Its phytochemistry mainly shows the presence of flavonoids and terpenoids such as monoterpenes, sesquiterpenes, diterpenes, and triterpenes. Some of them have been evaluated for biological activities presenting allelopathic, antimicrobial, cytotoxic, and anti-inflammatory properties. In this paper, our research group reported the isolation, characterization, and antifungal evaluation of several molecules isolated from the dichloromethane extract from Baccharis prunifolia, Baccharis trinervis, and Baccharis zumbadorensis against the phytopathogen fungus Botrytis cinerea. The isolated compounds have not previously been tested against Botrytis, revealing an important source of antifungals in the genus Baccharis. Six known flavones were isolated from B. prunifolia. The dichloromethane extracts of B. trinervis and B. zumbadorensis were subjected to a bio-guided isolation, obtaining three known flavones, an α-hydroxidihydrochalcone mixture, one labdane, one triterpene, and two norbisabolenes from the most active fractions. The compounds 4′-methoxy-α-hydroxydihydrochalcone (7A), 3β,15-dihydroxylabdan-7-en-17-al (8), and 13-nor-11,12-dihydroxybisabol-2-enone (11) are novel. The most active compounds were the Salvigenin (5) and 1,2-dihydrosenedigital-2-one (10) with an IC50 of 13.5 and 3.1 μg/mL, respectively. Full article
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14 pages, 926 KiB  
Review
Genetic Polymorphism in Angiotensinogen and Its Association with Cardiometabolic Diseases
by Momina Shahid, Kanwal Rehman, Muhammad Sajid Hamid Akash, Shaleem Suhail, Shagufta Kamal, Muhammad Imran and Mohammed A. Assiri
Metabolites 2022, 12(12), 1291; https://doi.org/10.3390/metabo12121291 - 19 Dec 2022
Cited by 13 | Viewed by 2806
Abstract
Angiotensinogen (AGT) is one of the most significant enzymes of the renin-angiotensin-aldosterone system (RAAS) which is involved in the regulation and maintenance of blood pressure. AGT is involved in the production of angiotensin I which is then converted into angiotensin II that leads [...] Read more.
Angiotensinogen (AGT) is one of the most significant enzymes of the renin-angiotensin-aldosterone system (RAAS) which is involved in the regulation and maintenance of blood pressure. AGT is involved in the production of angiotensin I which is then converted into angiotensin II that leads to renal homeostasis. However, various genetic polymorphisms in AGT have been discovered in recent times which have shown an association with various diseases. Genetic polymorphism increases the level of circulating AGT in blood which exaggerates the effects produced by AGT. The associated diseases occur due to various effects produced by increased AGT levels. Several cardiovascular diseases including myocardial infarction, coronary heart disease, heart failure, hypertrophy, etc. are associated with AGT polymorphism. Other diseases such as depression, obesity, diabetic nephropathy, pre-eclampsia, and liver injury are also associated with some variants of AGT gene. The most common variants of AGT polymorphism are M235T and T174M. The two variants are associated with many diseases. Some other variants such as G-217A, A-6G, A-20C and G-152A, are also present but they are not as significant as that of M235T and T174M variants. These variants increase the level of circulating AGT and are associated with prevalence of different diseases. These diseases occur through various pathological pathways, but the initial reason remains the same, i.e., increased level of AGT in the blood. In this article, we have majorly focused on how genetic polymorphism of different variants of AGT gene is associated with the prevalence of different diseases. Full article
(This article belongs to the Special Issue Biochemical Activation and Functions of Drug-Metabolizing Enzymes)
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17 pages, 3961 KiB  
Article
Transcription and Metabolism Pathways of Anthocyanin in Purple Shamrock (Oxalis triangularis A.St.-Hil.)
by Baobing Luo, Liujun Chen, Guoping Chen, Yunshu Wang, Qiaoli Xie, Xuqing Chen and Zongli Hu
Metabolites 2022, 12(12), 1290; https://doi.org/10.3390/metabo12121290 - 19 Dec 2022
Cited by 4 | Viewed by 1753
Abstract
Anthocyanins are water-soluble pigments that can impart various colors to plants. Purple shamrock (Oxalis triangularis) possesses unique ornamental value due to its purple leaves. In this study, three anthocyanins, including malvidin 3-O-(4-O-(6-O-malonyl-glucopyranoside)-rhamnopyranosyl)-5-O-(6-O-malonyl-glucopyranoside), delphinidin-3-O-rutinoside and malvidin-3,5-di-O-glucoside, were characterized with ultra-performance liquid chromatography-electrospray [...] Read more.
Anthocyanins are water-soluble pigments that can impart various colors to plants. Purple shamrock (Oxalis triangularis) possesses unique ornamental value due to its purple leaves. In this study, three anthocyanins, including malvidin 3-O-(4-O-(6-O-malonyl-glucopyranoside)-rhamnopyranosyl)-5-O-(6-O-malonyl-glucopyranoside), delphinidin-3-O-rutinoside and malvidin-3,5-di-O-glucoside, were characterized with ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) in purple shamrock. To investigate the molecular mechanism of anthocyanin biosynthesis in green shamrock (Oxalis corymbosa) and purple shamrock, RNA-seq and qRT-PCR were performed, and the results showed that most of the anthocyanin biosynthetic and regulatory genes were up-regulated in purple shamrock. Then, dark treatment and low temperature treatment experiments in purple shamrock showed that both light and low temperature can induce the biosynthesis of anthocyanins. Full article
(This article belongs to the Special Issue Plant Metabolic Genetic Engineering)
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13 pages, 2995 KiB  
Article
Metabolomic Analysis Reveals the Effect of Insecticide Chlorpyrifos on Rice Plant Metabolism
by Qi’er Mu, Mingxia Zhang, Yong Li, Fayun Feng, Xiangyang Yu and Jinfang Nie
Metabolites 2022, 12(12), 1289; https://doi.org/10.3390/metabo12121289 - 19 Dec 2022
Cited by 8 | Viewed by 1776
Abstract
Pesticides as important agricultural inputs play a vital role in protecting crop plants from diseases and pests; however, the effect of pesticides on crop plant physiology and metabolism is still undefined. In this study, the effect of insecticide chlorpyrifos at three doses on [...] Read more.
Pesticides as important agricultural inputs play a vital role in protecting crop plants from diseases and pests; however, the effect of pesticides on crop plant physiology and metabolism is still undefined. In this study, the effect of insecticide chlorpyrifos at three doses on rice plant physiology and metabolism was investigated. Our results revealed that chlorpyrifos cause oxidative stress in rice plants and even inhibit plant growth and the synthesis of protein and chlorophyll at high doses. The metabolomic results suggested that chlorpyrifos could affect the metabolic profiling of rice tissues and a total of 119 metabolites with significant changes were found, mainly including organic acids, amino acids, lipids, polyphenols, and flavonoids. Compared to the control, the content of glutamate family amino acids were significantly disturbed by chlorpyrifos, where defense-related proline and glutathione were significantly increased; however, glutamic acid, N-acetyl-glutamic acid and N-methyl-glutamic acid were significantly decreased. Many unsaturated fatty acids, such as linolenic acid and linoleic acid, and their derivatives lysophospholipids and phospholipids, were significantly accumulated in chlorpyrifos groups, which could act as osmolality substances to help rice cells relieve chlorpyrifos stress. Three organic acids, aminobenzoic acid, quinic acid, and phosphoenolpyruvic acid, involved in plant defenses, were significantly accumulated with the fold change ranging from 1.32 to 2.19. In addition, chlorpyrifos at middle- and high-doses caused the downregulation of most flavonoids. Our results not only revealed the effect of insecticide chlorpyrifos on rice metabolism, but also demonstrated the value of metabolomics in elucidating the mechanisms of plant responses to stresses. Full article
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16 pages, 1310 KiB  
Review
Ketogenic Diet and Vitamin D Metabolism: A Review of Evidence
by Paraskevi Detopoulou, Sousana K. Papadopoulou, Gavriela Voulgaridou, Vasileios Dedes, Despoina Tsoumana, Aristea Gioxari, George Gerostergios, Maria Detopoulou and George I. Panoutsopoulos
Metabolites 2022, 12(12), 1288; https://doi.org/10.3390/metabo12121288 - 19 Dec 2022
Cited by 6 | Viewed by 4928
Abstract
The ketogenic diet (KD), which is low in carbohydrates and high to normal in fat and protein, has been traditionally used in epilepsy for the last 100 years. More recently, its application in obesity has been introduced. The present review aimed to investigate [...] Read more.
The ketogenic diet (KD), which is low in carbohydrates and high to normal in fat and protein, has been traditionally used in epilepsy for the last 100 years. More recently, its application in obesity has been introduced. The present review aimed to investigate the effects of the KD on vitamin D. In total, five studies were done in healthy adults, one in subjects with type 2 diabetes, and seven in subjects with epilepsy that assessed the levels of vitamin D pre- and post-intervention. In the majority of studies, increases in circulating vitamin D were reported. The relationship of the KD with vitamin D was explained through several mechanisms: ketone bodies, macronutrient intake, the status levels of other fat-soluble vitamins, weight loss, changes in the hormonal milieu, and effects on gut microbiota. Moreover, potential nutrient–gene-related interactions were discussed. There is still a need to conduct multiple arm studies to compare the effects of the KD versus other diets and better decipher the particular effects of the KD on vitamin D levels and metabolism. Moreover, differentiations of the diet’s effects according to sex and genetic makeup should be investigated to prescribe KDs on a more personalized basis. Full article
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14 pages, 1507 KiB  
Article
Long-Term Impacts of Diurnal Temperature Range on Mortality and Cardiovascular Disease: A Nationwide Prospective Cohort Study
by Haosu Tang, Xin Wang, Yuting Kang, Congyi Zheng, Xue Cao, Yixin Tian, Zhen Hu, Linfeng Zhang, Zuo Chen, Yuxin Song, Runqing Gu, Jiayin Cai, Gang Huang and Zengwu Wang
Metabolites 2022, 12(12), 1287; https://doi.org/10.3390/metabo12121287 - 19 Dec 2022
Cited by 8 | Viewed by 1773
Abstract
Previous studies have documented the associations between short-term diurnal temperature range (DTR) exposure and cardiovascular disease (CVD) via time-series analyses. However, the long-term impacts of DTR through a population-based prospective cohort have not been elucidated thoroughly. This study aimed to quantify the longitudinal [...] Read more.
Previous studies have documented the associations between short-term diurnal temperature range (DTR) exposure and cardiovascular disease (CVD) via time-series analyses. However, the long-term impacts of DTR through a population-based prospective cohort have not been elucidated thoroughly. This study aimed to quantify the longitudinal association of DTR exposure with all-cause mortality and CVD in a nationwide prospective cohort and, by extension, project future DTR changes across China under climate change. We included 22,702 adults (median age 56.1 years, 53.7% women) free of CVD at baseline from a nationwide cross-sectional study in China during 2012–2015, and examined three health outcomes during a follow-up survey in 2018–2019. We estimated the chronic DTR exposure as baseline annual mean daily maximum minus minimum temperature. The Cox proportional hazards regression was adopted to assess the multivariable-adjusted hazard ratio and its corresponding 95% confidence interval (95% CI). We employed 31 downscaled global climate models under two shared socioeconomic pathways for future projection. During the median follow-up period of ~5 years, 1096 subjects died due to all causes while 993 and 597 individuals developed fatal or nonfatal CVD and fatal or nonfatal stroke, respectively. The cumulative incidence rates of all-cause mortality, CVD, and stroke were 10.49, 9.45, and 5.64 per 1000 person-years, respectively. In the fully adjusted models, the risks for all-cause mortality, CVD, and stroke would increase by 13% (95% CI: 8–18%), 12% (95% CI: 7–18%), and 9% (95% CI: 2–16%) per 1 °C increment in DTR, respectively. Moreover, linear positive associations for the concentration–response curves between DTR and mortality and CVD were observed. We also found significantly greater DTR-related mortality risks among rural residents than their urban counterparts. The DTR changes featured a dipole pattern across China under a warming climate. The southern (northern) China would experience increased (decreased) DTR exposure by the end of 21st century. The present study indicates that chronic DTR exposure can exert long-term impacts on mortality and CVD risks, which may inform future public health policies on DTR-related susceptible population and regions. Full article
(This article belongs to the Special Issue Environmental Exposures and Cardiovascular Disease)
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15 pages, 665 KiB  
Protocol
Efficacy of Different Modalities and Frequencies of Physical Exercise on Glucose Control in People with Prediabetes (GLYCEX Randomised Trial)
by Aina M Galmes-Panades, Miquel Bennasar-Veny, Paula Oliver, Natalia Garcia-Coll, Alice Chaplin, Sergio Fresneda, Laura Gallardo-Alfaro, Carmen García-Ruano, Jadwiga Konieczna, Alfonso Leiva, Lluis Masmiquel, Catalina Pico, Ignacio Ricci-Cabello, Dora Romaguera, Rosmeri Rivera, Pilar Sanchis, Josep Vidal-Conti and Aina M Yañez
Metabolites 2022, 12(12), 1286; https://doi.org/10.3390/metabo12121286 - 17 Dec 2022
Cited by 3 | Viewed by 2492
Abstract
To assess the efficacy of different modalities and frequencies of physical exercise on glycaemic control in adults with prediabetes. A two-phase, parallel, randomised, controlled clinical trial will be carried out, in 210 participants. In phase 1, 120 participants will be randomized into four [...] Read more.
To assess the efficacy of different modalities and frequencies of physical exercise on glycaemic control in adults with prediabetes. A two-phase, parallel, randomised, controlled clinical trial will be carried out, in 210 participants. In phase 1, 120 participants will be randomized into four arms: (1) aerobic exercise, (2) aerobic exercise combined with resistance, (3) high-intensity intervallic exercise and (4) control group. In phase 2, 90 new participants will be randomized into three arms, using the exercise modality that showed the best glycaemic control in phase 1 in the following manner: (1) frequency of 5 days/week, (2) frequency of 3 days/week and (3) frequency of 2 days/week. The control group (n = 30) will be included in phase 1 to evaluate the effect of any type of intervention versus no intervention. Data collection will be performed at baseline and after 15 weeks of follow up. Sociodemographic data, medication, comorbidity, blood biochemical parameters, blood pressure, anthropometric measurements, body composition, physical activity, sedentary lifestyle, diet, smoking, alcohol consumption, quality of life and sleep questionnaires will be collected. Physical activity, sedentary behaviour and sleep will be further determined with an accelerometer, and continuous glycaemia will be determined with a glycaemic monitor, both during seven days, at two time points. The main dependent variable will be the reduction in the mean amplitude of glycaemic excursions. The impact of these interventions on health will also be evaluated through gene expression analysis in peripheral blood cells. The results of this study will contribute to a better understanding of the mechanisms behind the glucose response to physical exercise in a population with prediabetes as well as improve physical exercise prescriptions for diabetes prevention. Increasing glycaemic control in people with prediabetes through physical exercise offers an opportunity to prevent diabetes and reduce associated comorbidities and health costs. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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12 pages, 3320 KiB  
Article
An Efficient and Economical N-Glycome Sample Preparation Using Acetone Precipitation
by Junyao Wang, Wenjing Peng, Mojibola Fowowe, Oluwatosin Daramola and Yehia Mechref
Metabolites 2022, 12(12), 1285; https://doi.org/10.3390/metabo12121285 - 17 Dec 2022
Cited by 4 | Viewed by 2161
Abstract
Due to the critical role of the glycome in organisms and its close connections with various diseases, much time and effort have been dedicated to glycomics-related studies in the past decade. To achieve accurate and reliable identification and quantification of glycans extracted from [...] Read more.
Due to the critical role of the glycome in organisms and its close connections with various diseases, much time and effort have been dedicated to glycomics-related studies in the past decade. To achieve accurate and reliable identification and quantification of glycans extracted from biological samples, several analysis methods have been well-developed. One commonly used methodology for the sample preparation of N-glycomics usually involves enzymatic cleavage by PNGase F, followed by sample purification using C18 cartridges to remove proteins. PNGase F and C18 cartridges are very efficient both for cleaving N-glycans and for protein removal. However, this method is most suitable for a limited quantity of samples. In this study, we developed a sample preparation method focusing on N-glycome extraction and purification from large-scale biological samples using acetone precipitation. The N-glycan yield was first tested on standard glycoprotein samples, bovine fetuin and complex biological samples, and human serum. Compared to C18 cartridges, most of the sialylated N-glycans from human serum were detected with higher abundance after acetone precipitation. However, C18 showed a slightly higher efficiency for protein removal. Using the unfiltered human serum as the baseline, around 97.7% of the proteins were removed by acetone precipitation, while more than 99.9% of the proteins were removed by C18 cartridges. Lastly, the acetone precipitation was applied to N-glycome extraction from egg yolks to demonstrate large-scale glycomics sample preparation. Full article
(This article belongs to the Section Nutrition and Metabolism)
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6 pages, 745 KiB  
Perspective
Cancer Cachexia and Dysregulated Phosphate Metabolism: Insights from Mutant p53 and Mutant Klotho Mouse Models
by Ronald B. Brown
Metabolites 2022, 12(12), 1284; https://doi.org/10.3390/metabo12121284 - 17 Dec 2022
Cited by 5 | Viewed by 1575
Abstract
The present perspective article proposes that cachexia, muscle wasting in cancer, is mediated by dysregulated phosphate metabolism and phosphate toxicity that can damage tissues in most major organ systems. A diet high in phosphorus fed to mice deficient in klotho, a cofactor that [...] Read more.
The present perspective article proposes that cachexia, muscle wasting in cancer, is mediated by dysregulated phosphate metabolism and phosphate toxicity that can damage tissues in most major organ systems. A diet high in phosphorus fed to mice deficient in klotho, a cofactor that regulates phosphate metabolism, accelerates aging, sarcopenia, general organ atrophy, kyphosis, and osteoporosis. Similar effects are seen in phenotypes of mutant p53 mice that overexpress the p53 tumor suppressor gene. Although mutant p53 mice do not develop tumors compared to wild-type mice, mutant p53 mice have shorter mean lifespans. Furthermore, tumorigenesis is associated with the sequestration of excessive inorganic phosphate, and dangerous levels of phosphate are released into circulation during tumor lysis syndrome. In total, this evidence implies that tumorigenesis may be a compensatory mechanism that provides protective effects against systemic exposure to dysregulated phosphate metabolism and phosphate toxicity related to cachexia in cancer. Moreover, the hypothetical protection against phosphate toxicity afforded by tumorigenesis also provides an alternate explanation for putative tumor evasion of the immune system. Insights proposed in this perspective paper provide new directions for further research, with potential to develop novel interventions and clinical applications that modify dietary phosphate intake to reduce cachexia in cancer patients. Full article
(This article belongs to the Special Issue Is Cancer a Metabolic Disease? The Answer of Metabolomics Volume 2)
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11 pages, 1804 KiB  
Article
Urinary Metabolomics in Young Soccer Players after Winter Training Season
by Hyang-Yeon Kim, Jung-Dae Lee, Yun-Hwan Lee, Sang-Won Seo, Ho-Seong Lee, Suhkmann Kim and Kyu-Bong Kim
Metabolites 2022, 12(12), 1283; https://doi.org/10.3390/metabo12121283 - 17 Dec 2022
Cited by 3 | Viewed by 1427
Abstract
During the off-season, soccer players in Korea attend the winter training season (WTS) to build running stamina for the next season. For young soccer players, proper recovery time is needed to prevent injury or muscle damage. In this study, urinary metabolites in young [...] Read more.
During the off-season, soccer players in Korea attend the winter training season (WTS) to build running stamina for the next season. For young soccer players, proper recovery time is needed to prevent injury or muscle damage. In this study, urinary metabolites in young players after 1, 5, and 10 days of the WTS were analyzed using nuclear magnetic resonance spectroscopy (NMR) combined with multivariate analysis to suggest appropriate recovery times for improving their soccer skills. After NMR analysis of the urine samples obtained from young players, 79 metabolites were identified, and each group (1, 5, or 10 days after WTS) was separated from the before the WTS group in the target profiling analysis using partial least squares-discriminant analysis (PLS-DA). Of these, 15 metabolites, including 1-methylnicotinamide, 3-indoxylsulfate, galactarate, glutamate, glycerol, histamine, methylmalonate, maltose, N-phenylacetylglycine, trimethylamine, urea, 2-hydroxybutyrate, adenine, alanine, and lactate, were significantly different than those from before the WTS and were mainly involved in the urea, purine nucleotide, and glucose-alanine cycles. In this study, most selected metabolites increased 1 day after the WTS and then returned to normal levels. However, 4 metabolites, adenine, 2-hydroxybutyrate, alanine, and lactate, increased during the 5 days of recovery time following the WTS. Based on excess ammonia, adenine, and lactate levels in the urine, at least 5 days of recovery time can be considered appropriate. Full article
(This article belongs to the Section Cell Metabolism)
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18 pages, 1329 KiB  
Article
Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia
by Marina Darenskaya, Elena Chugunova, Sergey Kolesnikov, Natalya Semenova, Isay Michalevich, Olga Nikitina, Anastasya Lesnaya and Lyubov Kolesnikova
Metabolites 2022, 12(12), 1282; https://doi.org/10.3390/metabo12121282 - 16 Dec 2022
Cited by 5 | Viewed by 1479
Abstract
Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of [...] Read more.
Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30–300 mg/day and albumin/creatinine ratio 3–30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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34 pages, 3915 KiB  
Article
Optimising Fluvoxamine Maternal/Fetal Exposure during Gestation: A Pharmacokinetic Virtual Clinical Trials Study
by Khairulanwar Burhanuddin and Raj Badhan
Metabolites 2022, 12(12), 1281; https://doi.org/10.3390/metabo12121281 - 16 Dec 2022
Cited by 2 | Viewed by 1831
Abstract
Fluvoxamine plasma concentrations have been shown to decrease throughout pregnancy. CYP2D6 polymorphisms significantly influence these changes. However, knowledge of an optimum dose adjustment according to the CYP2D6 phenotype is still limited. This study implemented a physiologically based pharmacokinetic modelling approach to assess the [...] Read more.
Fluvoxamine plasma concentrations have been shown to decrease throughout pregnancy. CYP2D6 polymorphisms significantly influence these changes. However, knowledge of an optimum dose adjustment according to the CYP2D6 phenotype is still limited. This study implemented a physiologically based pharmacokinetic modelling approach to assess the gestational changes in fluvoxamine maternal and umbilical cord concentrations. The optimal dosing strategies during pregnancy were simulated, and the impact of CYP2D6 phenotypes on fluvoxamine maternal and fetal concentrations was considered. A significant decrease in fluvoxamine maternal plasma concentrations was noted during gestation. As for the fetal concentration, a substantial increase was noted for the poor metabolisers (PM), with a constant level in the ultrarapid (UM) and extensive (EM) metabolisers commencing from gestation week 20 to term. The optimum dosing regimen suggested for UM and EM reached a maximum dose of 300 mg daily at gestational weeks (GW) 15 and 35, respectively. In contrast, a stable dose of 100 mg daily throughout gestation for the PM is sufficient to maintain the fluvoxamine plasma concentration within the therapeutic window (60–230 ng/mL). Dose adjustment during pregnancy is required for fluvoxamine, particularly for UM and EM, to maintain efficacy throughout the gestational period. Full article
(This article belongs to the Special Issue Fetal–Maternal–Neonatal Metabolomics)
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29 pages, 2402 KiB  
Systematic Review
Lipid Alterations in Glioma: A Systematic Review
by Khairunnisa Abdul Rashid, Kamariah Ibrahim, Jeannie Hsiu Ding Wong and Norlisah Mohd Ramli
Metabolites 2022, 12(12), 1280; https://doi.org/10.3390/metabo12121280 - 16 Dec 2022
Cited by 7 | Viewed by 2173
Abstract
Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid metabolism reprogramming is predominant and has contributed to the metabolic plasticity in glioma. This systematic review aims to discover lipids alteration and their biological [...] Read more.
Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid metabolism reprogramming is predominant and has contributed to the metabolic plasticity in glioma. This systematic review aims to discover lipids alteration and their biological roles in glioma and the identification of potential lipids biomarker. This systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Extensive research articles search for the last 10 years, from 2011 to 2021, were conducted using four electronic databases, including PubMed, Web of Science, CINAHL and ScienceDirect. A total of 158 research articles were included in this study. All studies reported significant lipid alteration between glioma and control groups, impacting glioma cell growth, proliferation, drug resistance, patients’ survival and metastasis. Different lipids demonstrated different biological roles, either beneficial or detrimental effects on glioma. Notably, prostaglandin (PGE2), triacylglycerol (TG), phosphatidylcholine (PC), and sphingosine-1-phosphate play significant roles in glioma development. Conversely, the most prominent anti-carcinogenic lipids include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and vitamin D3 have been reported to have detrimental effects on glioma cells. Furthermore, high lipid signals were detected at 0.9 and 1.3 ppm in high-grade glioma relative to low-grade glioma. This evidence shows that lipid metabolisms were significantly dysregulated in glioma. Concurrent with this knowledge, the discovery of specific lipid classes altered in glioma will accelerate the development of potential lipid biomarkers and enhance future glioma therapeutics. Full article
(This article belongs to the Special Issue Unravel Metabolism and Resistance Mechanisms in Glioblastoma)
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9 pages, 260 KiB  
Article
Parameters of Vitamin D Metabolism in Patients with Hypoparathyroidism
by Artem Zhukov, Alexandra Povaliaeva, Zaur Abilov, Elena Kovaleva, Liliya Usoltseva, Anna Eremkina, Vitaliy Ioutsi, Larisa Dzeranova, Ekaterina Pigarova, Liudmila Rozhinskaya and Natalia Mokrysheva
Metabolites 2022, 12(12), 1279; https://doi.org/10.3390/metabo12121279 - 16 Dec 2022
Cited by 3 | Viewed by 1615
Abstract
Only a few studies evaluating the metabolism of vitamin D in patients with hypoparathyroidism (HypoPT) have been performed thus far, and, in particular, they mainly investigated the process of vitamin D activation (specifically, 1α-hydroxylation). This study, therefore, aimed to evaluate the extended spectrum [...] Read more.
Only a few studies evaluating the metabolism of vitamin D in patients with hypoparathyroidism (HypoPT) have been performed thus far, and, in particular, they mainly investigated the process of vitamin D activation (specifically, 1α-hydroxylation). This study, therefore, aimed to evaluate the extended spectrum of vitamin D metabolites in patients with HypoPT compared to healthy individuals. We examined 38 adult patients with chronic HypoPT in comparison to 38 healthy adults. The assessment included biochemical parameters (total calcium, albumin, phosphorus, creatinine, and magnesium), parathyroid hormone (PTH), and vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3) in serum. Our data show that an adequate level of 25(OH)D3 (median 35.3 (29.6; 42.0) ng/mL) is achieved with standard doses of cholecalciferol (median 2000 (2000; 2500) IU per day) in HypoPT patients. They also presented with supraphysiological levels of 1,25(OH)2D3 (median 71 (47; 96) vs. 40 (34; 59) pg/mL, p < 0.001) and the increased production of inactive metabolite (median 24,25(OH)2D3 3.8 (3.0; 5.1) vs. 1.9 (1.3; 2.7) ng/mL, p < 0.001; median 25(OH)D3/24,25(OH)2D3 ratio 8.9 (7.6; 11.1) vs. 13.5 (11.1; 17.0), p < 0.001) as compared to the control group. This might be a consequence of the therapy received (treatment with activated vitamin D) and the pathophysiology of the disease (lack of PTH). The abnormality of vitamin D metabolism does not seem to interfere with the achievement of hypoparathyroidism compensation. Full article
(This article belongs to the Special Issue Metabolic and Functional Disorders of Essential Metals and Vitamin D)
13 pages, 12638 KiB  
Article
1H-NMR-Based Metabonomics Study to Reveal the Progressive Metabolism Regulation of SAP Deficiency on ApoE−/− Mice
by Qian Li, Wanting Chen, Wenbin Huang, Ranran Hou, Xinping Huang, Man Xu, Limei Que, Lijing Wang and Yongxia Yang
Metabolites 2022, 12(12), 1278; https://doi.org/10.3390/metabo12121278 - 16 Dec 2022
Viewed by 1377
Abstract
Atherosclerosis is the most common disease of the vascular system and the metabolic disorder is one of its important molecular mechanisms. SAP protein is found to be highly expressed in atherosclerotic blood vessels. Our previous study found that SAP deficiency can significantly inhibit [...] Read more.
Atherosclerosis is the most common disease of the vascular system and the metabolic disorder is one of its important molecular mechanisms. SAP protein is found to be highly expressed in atherosclerotic blood vessels. Our previous study found that SAP deficiency can significantly inhibit the development of atherosclerosis. However, the regulatory effect of SAP deficiency on AS metabolism is unknown. Based on 1H-NMR metabonomics, this study investigated the serum metabolic changes in ApoE−/−;SAP−/− mice compared with ApoE−/− mice during the whole progression of atherosclerosis. The results showed that acetate, pyruvate, choline and VLDL + LDL were statistically regulated to the normal levels as in C57 mice by SAP deficiency in ApoE−/−;SAP−/− mice at 8 w (without obvious plaques). With the appearance and aggravation of atherosclerotic plaques (8 + 4 w and 8 + 8 w), the four metabolites of acetate, pyruvate, choline and VLDL + LDL were continuously regulated, which were denoted as the metabolic regulatory markers of SAP deficiency. We also found that the changes in these four metabolites had nothing to do with high-fat diet. Therefore, it was revealed that SAP deficiency regulated the metabolic disorders in ApoE−/− prior to the appearance of obvious atherosclerotic plaques, which is one of the important mechanisms leading to the inhibition of atherosclerosis, providing a new basis for the application of SAP in atherosclerosis. Full article
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29 pages, 38102 KiB  
Article
Quantitative Serum NMR Spectroscopy Stratifies COVID-19 Patients and Sheds Light on Interfaces of Host Metabolism and the Immune Response with Cytokines and Clinical Parameters
by Titus Rössler, Georgy Berezhnoy, Yogesh Singh, Claire Cannet, Tony Reinsperger, Hartmut Schäfer, Manfred Spraul, Manfred Kneilling, Uta Merle and Christoph Trautwein
Metabolites 2022, 12(12), 1277; https://doi.org/10.3390/metabo12121277 - 16 Dec 2022
Cited by 10 | Viewed by 2514
Abstract
The complex manifestations of COVID-19 are still not fully decoded on the molecular level. We combined quantitative the nuclear magnetic resonance (NMR) spectroscopy serum analysis of metabolites, lipoproteins and inflammation markers with clinical parameters and a targeted cytokine panel to characterize COVID-19 in [...] Read more.
The complex manifestations of COVID-19 are still not fully decoded on the molecular level. We combined quantitative the nuclear magnetic resonance (NMR) spectroscopy serum analysis of metabolites, lipoproteins and inflammation markers with clinical parameters and a targeted cytokine panel to characterize COVID-19 in a large (534 patient samples, 305 controls) outpatient cohort of recently tested PCR-positive patients. The COVID-19 cohort consisted of patients who were predominantly in the initial phase of the disease and mostly exhibited a milder disease course. Concerning the metabolic profiles of SARS-CoV-2-infected patients, we identified markers of oxidative stress and a severe dysregulation of energy metabolism. NMR markers, such as phenylalanine, inflammatory glycoproteins (Glyc) and their ratio with the previously reported supramolecular phospholipid composite (Glyc/SPC), showed a predictive power comparable to laboratory parameters such as C-reactive protein (CRP) or ferritin. We demonstrated interfaces between the metabolism and the immune system, e.g., we could trace an interleukin (IL-6)-induced transformation of a high-density lipoprotein (HDL) to a pro-inflammatory actor. Finally, we showed that metadata such as age, sex and constitution (e.g., body mass index, BMI) need to be considered when exploring new biomarkers and that adding NMR parameters to existing diagnoses expands the diagnostic toolbox for patient stratification and personalized medicine. Full article
(This article belongs to the Special Issue Advances in Understanding Altered Metabolism in SARS-CoV-2 Infection)
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23 pages, 25428 KiB  
Article
Identification of a Chromosome 1 Substitution Line B6-Chr1BLD as a Novel Hyperlipidemia Model via Phenotyping Screening
by Xu Li, Minli Sun, Hao Qi, Cunxiang Ju, Zhong Chen, Xiang Gao and Zhaoyu Lin
Metabolites 2022, 12(12), 1276; https://doi.org/10.3390/metabo12121276 - 16 Dec 2022
Cited by 1 | Viewed by 1871
Abstract
Hyperlipidemia is a chronic disease that seriously affects human health. Due to the fact that traditional animal models cannot fully mimic hyperlipidemia in humans, new animal models are urgently needed for basic drug research on hyperlipidemia. Previous studies have demonstrated that the genomic [...] Read more.
Hyperlipidemia is a chronic disease that seriously affects human health. Due to the fact that traditional animal models cannot fully mimic hyperlipidemia in humans, new animal models are urgently needed for basic drug research on hyperlipidemia. Previous studies have demonstrated that the genomic diversity of the wild mice chromosome 1 substitution lines was significantly different from that of laboratory mice, suggesting that it might be accompanied by phenotypic diversity. We first screened the blood lipid-related phenotype of chromosome 1 substitution lines. We found that the male HFD-fed B6-Chr1BLD mice showed more severe hyperlipidemia-related phenotypes in body weight, lipid metabolism and liver lesions. By RNA sequencing and whole-genome sequencing results of B6-Chr1BLD, we found that several differentially expressed single nucleotide polymorphism enriched genes were associated with lipid metabolism-related pathways. Lipid metabolism-related genes, mainly including Aida, Soat1, Scly and Ildr2, might play an initial and upstream role in the abnormal metabolic phenotype of male B6-Chr1BLD mice. Taken together, male B6-Chr1BLD mice could serve as a novel, polygenic interaction-based hyperlipidemia model. This study could provide a novel animal model for accurate clinical diagnosis and precise medicine of hyperlipidemia. Full article
(This article belongs to the Special Issue The Role of Lipid Metabolism in Dyslipidemias and Atherosclerosis)
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10 pages, 2174 KiB  
Article
ConCISE: Consensus Annotation Propagation of Ion Features in Untargeted Tandem Mass Spectrometry Combining Molecular Networking and In Silico Metabolite Structure Prediction
by Zachary A. Quinlan, Irina Koester, Allegra T. Aron, Daniel Petras, Lihini I. Aluwihare, Pieter C. Dorrestein, Craig E. Nelson and Linda Wegley Kelly
Metabolites 2022, 12(12), 1275; https://doi.org/10.3390/metabo12121275 - 16 Dec 2022
Cited by 10 | Viewed by 2461
Abstract
Recent developments in molecular networking have expanded our ability to characterize the metabolome of diverse samples that contain a significant proportion of ion features with no mass spectral match to known compounds. Manual and tool-assisted natural annotation propagation is readily used to classify [...] Read more.
Recent developments in molecular networking have expanded our ability to characterize the metabolome of diverse samples that contain a significant proportion of ion features with no mass spectral match to known compounds. Manual and tool-assisted natural annotation propagation is readily used to classify molecular networks; however, currently no annotation propagation tools leverage consensus confidence strategies enabled by hierarchical chemical ontologies or enable the use of new in silico tools without significant modification. Herein we present ConCISE (Consensus Classifications of In Silico Elucidations) which is the first tool to fuse molecular networking, spectral library matching and in silico class predictions to establish accurate putative classifications for entire subnetworks. By limiting annotation propagation to only structural classes which are identical for the majority of ion features within a subnetwork, ConCISE maintains a true positive rate greater than 95% across all levels of the ChemOnt hierarchical ontology used by the ClassyFire annotation software (superclass, class, subclass). The ConCISE framework expanded the proportion of reliable and consistent ion feature annotation up to 76%, allowing for improved assessment of the chemo-diversity of dissolved organic matter pools from three complex marine metabolomics datasets comprising dominant reef primary producers, five species of the diatom genus Pseudo-nitzchia, and stromatolite sediment samples. Full article
(This article belongs to the Special Issue Marine Microbes Related Metabolic Studies)
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17 pages, 2385 KiB  
Review
Gingerol, a Natural Antioxidant, Attenuates Hyperglycemia and Downstream Complications
by Khalid Saad Alharbi, Muhammad Shahid Nadeem, Obaid Afzal, Sami I. Alzarea, Abdulmalik S. A. Altamimi, Waleed Hassan Almalki, Bismillah Mubeen, Saima Iftikhar, Luqman Shah and Imran Kazmi
Metabolites 2022, 12(12), 1274; https://doi.org/10.3390/metabo12121274 - 16 Dec 2022
Cited by 15 | Viewed by 3043
Abstract
Hyperglycemia is seen in approximately 68 percent of patients admitted to a medical intensive care unit (ICU). In many acute circumstances, such as myocardial infarction, brain, injury and stroke, it is an independent predictor of mortality. Hyperglycemia is induced by a mix of [...] Read more.
Hyperglycemia is seen in approximately 68 percent of patients admitted to a medical intensive care unit (ICU). In many acute circumstances, such as myocardial infarction, brain, injury and stroke, it is an independent predictor of mortality. Hyperglycemia is induced by a mix of genetic, environmental, and immunologic variables in people with type 1 diabetes. These factors cause pancreatic beta cell death and insulin insufficiency. Insulin resistance and irregular insulin production cause hyperglycemia in type 2 diabetes patients. Hyperglycemia activates a number of complicated interconnected metabolic processes. Hyperglycemia is a major contributor to the onset and progression of diabetes’ secondary complications such as neuropathy, nephropathy, retinopathy, cataracts, periodontitis, and bone and joint issues. Studies on the health benefits of ginger and its constituent’s impact on hyperglycemia and related disorders have been conducted and gingerol proved to be a potential pharmaceutically active constituent of ginger (Zingiber officinale) that has been shown to lower blood sugar levels, because it possesses antioxidant properties and it functions as an antioxidant in the complicated biochemical process that causes hyperglycemia to be activated. Gingerol not only helps in treating hyperglycemia but also shows effectivity against diseases related to it, such as cardiopathy, kidney failure, vision impairments, bone and joint problems, and teeth and gum infections. Moreover, fresh ginger has various gingerol analogues, with 6-gingerol being the most abundant. However, it is necessary to investigate the efficacy of its other analogues against hyperglycemia and associated disorders at various concentrations in order to determine the appropriate dose for treating these conditions. Full article
(This article belongs to the Special Issue Dietary Antioxidants and Metabolic Diseases)
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18 pages, 487 KiB  
Systematic Review
The Effect of Diet on the Cardiac Circadian Clock in Mice: A Systematic Review
by Ana Beatriz Rezende Paula, Letícia Teresinha Resende, Isabela Alcântara Barretto Araújo Jardim, Bianca Iara Campos Coelho, Denise de Coutinho Miranda, Alexandre Martins Oliveira Portes, Maria Cecília Teles, Ana Maria de Lauro Castrucci and Mauro César Isoldi
Metabolites 2022, 12(12), 1273; https://doi.org/10.3390/metabo12121273 - 15 Dec 2022
Cited by 1 | Viewed by 2128
Abstract
Circadian rhythms play important roles in regulating physiological and behavioral processes. These are adjusted by environmental cues, such as diet, which acts by synchronizing or attenuating the circadian rhythms of peripheral clocks, such as the liver, intestine, pancreas, white and brown adipose tissue, [...] Read more.
Circadian rhythms play important roles in regulating physiological and behavioral processes. These are adjusted by environmental cues, such as diet, which acts by synchronizing or attenuating the circadian rhythms of peripheral clocks, such as the liver, intestine, pancreas, white and brown adipose tissue, lungs, kidneys, as well as the heart. Some studies point to the influence of diet composition, feeding timing, and dietary restriction on metabolic homeostasis and circadian rhythms at various levels. Therefore, this systematic review aimed to discuss studies addressing the effect of diet on the heart clock in animal models and, additionally, the chronodisruption of the clock and its relation to the development of cardiovascular disorders in the last 15 years. A search was conducted in the PubMed, Scopus, and Embase databases. The PRISMA guide was used to construct the article. Nineteen studies met all inclusion and exclusion criteria. In summary, these studies have linked the circadian clock to cardiovascular health and suggested that maintaining a robust circadian system may reduce the risks of cardiometabolic and cardiovascular diseases. The effect of time-of-day-dependent eating on the modulation of circadian rhythms of the cardiac clock and energy homeostasis is notable, among its deleterious effects predominantly in the sleep (light) phase and/or at the end of the active phase. Full article
(This article belongs to the Special Issue Roles of the Circadian Rhythms in Metabolic Disease and Health)
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15 pages, 1705 KiB  
Article
Metabolomics and Lipidomics Signatures of Insulin Resistance and Abdominal Fat Depots in People Living with Obesity
by Yen Chin Koay, Adelle C. F. Coster, Daniel L. Chen, Brad Milner, Amani Batarseh, John F. O’Sullivan, Jerry R. Greenfield and Dorit Samocha-Bonet
Metabolites 2022, 12(12), 1272; https://doi.org/10.3390/metabo12121272 - 15 Dec 2022
Cited by 4 | Viewed by 1987
Abstract
The liver, skeletal muscle, and adipose tissue are major insulin target tissues and key players in glucose homeostasis. We and others have described diverse insulin resistance (IR) phenotypes in people at risk of developing type 2 diabetes. It is postulated that identifying the [...] Read more.
The liver, skeletal muscle, and adipose tissue are major insulin target tissues and key players in glucose homeostasis. We and others have described diverse insulin resistance (IR) phenotypes in people at risk of developing type 2 diabetes. It is postulated that identifying the IR phenotype in a patient may guide the treatment or the prevention strategy for better health outcomes in populations at risk. Here, we performed plasma metabolomics and lipidomics in a cohort of men and women living with obesity not complicated by diabetes (mean [SD] BMI 36.0 [4.5] kg/m2, n = 62) to identify plasma signatures of metabolites and lipids that align with phenotypes of IR (muscle, liver, or adipose tissue) and abdominal fat depots. We used 2-step hyperinsulinemic-euglycemic clamp with deuterated glucose, oral glucose tolerance test, dual-energy X-ray absorptiometry and abdominal magnetic resonance imaging to assess muscle-, liver- and adipose tissue- IR, beta cell function, body composition, abdominal fat distribution and liver fat, respectively. Spearman’s rank correlation analyses that passed the Benjamini–Hochberg statistical correction revealed that cytidine, gamma-aminobutyric acid, anandamide, and citrate corresponded uniquely with muscle IR, tryptophan, cAMP and phosphocholine corresponded uniquely with liver IR and phenylpyruvate and hydroxy-isocaproic acid corresponded uniquely with adipose tissue IR (p < 7.2 × 10−4). Plasma cholesteryl sulfate (p = 0.00029) and guanidinoacetic acid (p = 0.0001) differentiated between visceral and subcutaneous adiposity, while homogentisate correlated uniquely with liver fat (p = 0.00035). Our findings may help identify diverse insulin resistance and adiposity phenotypes and enable targeted treatments in people living with obesity. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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17 pages, 539 KiB  
Systematic Review
Impact of Diet on Gut Microbiota Composition and Microbiota-Associated Functions in Heart Failure: A Systematic Review of In Vivo Animal Studies
by Marta Palombaro, Pauline Raoul, Marco Cintoni, Emanuele Rinninella, Gabriele Pulcini, Nadia Aspromonte, Gianluca Ianiro, Antonio Gasbarrini and Maria Cristina Mele
Metabolites 2022, 12(12), 1271; https://doi.org/10.3390/metabo12121271 - 15 Dec 2022
Cited by 5 | Viewed by 1943
Abstract
Heart failure (HF) represents a cardiovascular disease with high mortality and morbidity. The latest evidence shows that changes in the composition of the gut microbiota might play a pivotal role in the prevention and management of HF. This systematic review aims at assessing [...] Read more.
Heart failure (HF) represents a cardiovascular disease with high mortality and morbidity. The latest evidence shows that changes in the composition of the gut microbiota might play a pivotal role in the prevention and management of HF. This systematic review aims at assessing the potential associations between the diet, gut microbiota, and derived metabolites with the outcomes of HF. A systematic literature search was performed up to July 2022 on the PubMed, Web of Science, and Scopus databases. The PRISMA guidelines were followed when possible. The risk of bias was assessed with the SYRCLE and ARRIVE tools. A total of nine pre-clinical studies on animal models, with considerable heterogeneity in dietary interventions, were included. High-fiber/prebiotic diets (n = 4) and a diet rich in polyphenols (n = 1) modified the gut microbiota composition and increased microbial metabolites’ activities, linked with an improvement in HF outcomes, such as a reduction in systolic blood pressure, cardiac hypertrophy, and left ventricular thickness. A high-fat diet (n = 2) or a diet rich in choline (n = 2) induced an increase in TMAO and indole derivative production associated with a decrease in cardiac function, systemic endotoxemia, and inflammation and an increase in cardiac fibrosis and cardiac remodeling. Although results are retrieved from animal studies, this systematic review shows the key role of the diet—especially a high-fiber and prebiotic diet—on gut microbial metabolites in improving HF outcomes. Further studies on human cohorts are needed to identify personalized therapeutic dietary interventions to improve cardiometabolic health. Full article
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17 pages, 2509 KiB  
Article
Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip
by Amal Essaouiba, Rachid Jellali, Françoise Gilard, Bertrand Gakière, Teru Okitsu, Cécile Legallais, Yasuyuki Sakai and Eric Leclerc
Metabolites 2022, 12(12), 1270; https://doi.org/10.3390/metabo12121270 - 15 Dec 2022
Cited by 1 | Viewed by 1766
Abstract
Diabetes mellitus (DM) is a complex disease with high prevalence of comorbidity and mortality. DM is predicted to reach more than 700 million people by 2045. In recent years, several advanced in vitro models and analytical tools were developed to investigate the pancreatic [...] Read more.
Diabetes mellitus (DM) is a complex disease with high prevalence of comorbidity and mortality. DM is predicted to reach more than 700 million people by 2045. In recent years, several advanced in vitro models and analytical tools were developed to investigate the pancreatic tissue response to pathological situations and identify therapeutic solutions. Of all the in vitro promising models, cell culture in microfluidic biochip allows the reproduction of in-vivo-like micro-environments. Here, we cultured rat islets of Langerhans using dynamic cultures in microfluidic biochips. The dynamic cultures were compared to static islets cultures in Petri. The islets’ exometabolomic signatures, with and without GLP1 and isradipine treatments, were characterized by GC-MS. Compared to Petri, biochip culture contributes to maintaining high secretions of insulin, C-peptide and glucagon. The exometabolomic profiling revealed 22 and 18 metabolites differentially expressed between Petri and biochip on Day 3 and 5. These metabolites illustrated the increase in lipid metabolism, the perturbation of the pentose phosphate pathway and the TCA cycle in biochip. After drug stimulations, the exometabolome of biochip culture appeared more perturbed than the Petri exometabolome. The GLP1 contributed to the increase in the levels of glycolysis, pentose phosphate and glutathione pathways intermediates, whereas isradipine led to reduced levels of lipids and carbohydrates. Full article
(This article belongs to the Special Issue Cellular Metabolism in the Omics Era)
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13 pages, 5877 KiB  
Article
Effect of Binding Linkers on the Efficiency and Metabolite Profile of Biomimetic Reactions Catalyzed by Immobilized Metalloporphyrin
by György T. Balogh, Balázs Decsi, Réka Krammer, Balázs Kenéz, Ferenc Ender, Tamás Hergert and Diána Balogh-Weiser
Metabolites 2022, 12(12), 1269; https://doi.org/10.3390/metabo12121269 - 15 Dec 2022
Viewed by 1301
Abstract
The investigation of liver-related metabolic stability of a drug candidate is a widely used key strategy in early-stage drug discovery. Metalloporphyrin-based biomimetic catalysts are good and well-described models of the function of CyP450 in hepatocytes. In this research, the immobilization of an iron [...] Read more.
The investigation of liver-related metabolic stability of a drug candidate is a widely used key strategy in early-stage drug discovery. Metalloporphyrin-based biomimetic catalysts are good and well-described models of the function of CyP450 in hepatocytes. In this research, the immobilization of an iron porphyrin was performed on nanoporous silica particles via ionic interactions. The effect of the metalloporphyrin binding linkers was investigated on the catalytic efficiency and the metabolic profile of chloroquine as a model drug. The length of the amino-substituted linkers affects the chloroquine conversion as well as the ratio of human major and minor metabolites. While testing the immobilized catalysts in the continuous-flow reactor, results showed that the presented biomimetic system could be a promising alternative for the early-stage investigation of drug metabolites regarding analytical or synthetic goals as well. Full article
(This article belongs to the Special Issue Drug Discovery Metabolism and Biotransformation)
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12 pages, 1528 KiB  
Article
Glycerol Monolaurate Alleviates Oxidative Stress and Intestinal Flora Imbalance Caused by Salinity Changes for Juvenile Grouper
by Xuehe Li, Dongwenjun Zhu, Minling Mao, Jianwei Wu, Qihui Yang, Beiping Tan and Shuyan Chi
Metabolites 2022, 12(12), 1268; https://doi.org/10.3390/metabo12121268 - 15 Dec 2022
Cited by 2 | Viewed by 1155
Abstract
Groupers with an initial body weight of 9.10 ± 0.03 g were selected to investigate whether dietary addition of 0 (G0) and 1800 mg/kg glycerol monolaurate (GML, G1800) could alleviate the oxidative stress response and intestinal flora imbalance after 0, 6, 12, and [...] Read more.
Groupers with an initial body weight of 9.10 ± 0.03 g were selected to investigate whether dietary addition of 0 (G0) and 1800 mg/kg glycerol monolaurate (GML, G1800) could alleviate the oxidative stress response and intestinal flora imbalance after 0, 6, 12, and 24 h of salinity change in grouper. Experimental results show that the dietary addition of GML significantly reduced the liver MDA content and increased the SOD activity of grouper. The gene expression of CAT and SOD increased and then decreased with time after adding 1800 mg/kg GML, and the highest values were significantly higher than those of the control group. Salinity change had a slight effect on the top four intestinal flora composition of grouper at 0, 12, and 24 h, with changes occurring only at 6 h when Cyanobacteria replaced Actinobacteria. The addition of dietary GML slowed down the intestinal flora disorder, inhibited the colonization of harmful bacterium Vibrio, and promoted the abundance of beneficial bacterium Bacillus. In conclusion, dietary GML significantly reduced the oxidative damage caused by sudden changes in salinity, improved the antioxidant capacity, and alleviated the intestinal flora imbalance in juvenile grouper. Full article
(This article belongs to the Special Issue Nutrient Metabolism and Intestinal Health Studies in Aquatic Animals)
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