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Bioactive Compounds and Metabolic Disease

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (25 October 2023) | Viewed by 14953

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Dr. Anna Pastore

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Guest Editor

Research Unit of Diagnostical and Management Innovations, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
Interests: oxidative stress; glutathione metabolism; low-molecular weight thiols; reactive oxygen species; antioxidants; neuroscience

Dr. Anna Alisi

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Guest Editor

Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
Interests: liver diseases; non-alcoholic fatty liver disease; hepatocellular carcinoma; epigenetic mechanisms; microRNAs
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Special Issue Information

Dear Colleagues,

Metabolic syndrome (MetS) is a complex disease including elevated blood lipids, hyperglycemia, insulin resistance, hypertension, and obesity. This cluster of conditions harm several organs, mainly the liver, cardiovascular system, pancreas, and kidney, thus promoting the development of MetS, accounting for almost 60% of global mortality. For this reason, the prevention and cure of MetS has become a priority for healthcare systems worldwide.

Food and nutrients play a dual role in MetS. Indeed, groups of food (junk foods, sugary snacks, and sugar-sweetened beverages) and the excessive intake of specific macronutrients (fatty acids and sugars) may contribute to the onset of MetS. On the other hand, several micronutrients (vitamins and polyphenols and their derivatives) may exert a neutralizing action, strongly limiting MetS progression and consequent multiorgan damage.

This Special Issue aims to discuss how food and nutrients may play a bad or a good role in the development, prevention, and treatment of MetS and its consequences. The comprehension of this duality is crucial for the management of these multifactorial diseases.

The Guest Editors welcome original contributions, epidemiological studies, narrative and systematic reviews, as well as meta-analyses that highlight both the pathogenetic and therapeutic role of foods and nutrients in MetS and co-morbidities.

Dr. Anna Pastore
Dr. Anna Alisi
Guest Editors

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Keywords

metabolic syndrome
antioxidant
micronutrients
macronutrients

Published Papers (9 papers)

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12 pages, 1551 KiB

Open AccessArticle

Yerba Maté (Ilex paraguariensis) Supplement Exerts Beneficial, Tissue-Specific Effects on Mitochondrial Efficiency and Redox Status in Healthy Adult Mice

by Chase M. Walton, Erin R. Saito, Cali E. Warren, John G. Larsen, Nicole P. Remund, Paul R. Reynolds, Jason M. Hansen and Benjamin T. Bikman

Nutrients 2023, 15(20), 4454; https://doi.org/10.3390/nu15204454 - 20 Oct 2023

Viewed by 2121

Abstract

Yerba maté, a herbal tea derived from Ilex paraguariensis, has previously been reported to be protective against obesity-related and other cardiometabolic disorders. Using high-resolution respirometry and reverse-phase high-performance liquid chromatography, the effects of four weeks of yerba maté consumption on mitochondrial efficiency and cellular redox status in skeletal muscle, adipose, and liver, tissues highly relevant to whole-body metabolism, were explored in healthy adult mice. Yerba maté treatment increased the mitochondrial oxygen consumption in adipose but not in the other examined tissues. Yerba maté increased the ATP concentration in skeletal muscle and decreased the ATP concentration in adipose. Combined with the observed changes in oxygen consumption, these data yielded a significantly higher ATP:O₂, a measure of mitochondrial efficiency, in muscle and a significantly lower ATP:O₂ in adipose, which was consistent with yerba maté-induced weight loss. Yerba maté treatment also altered the hepatic glutathione (GSH)/glutathione disulfide (GSSG) redox potential to a more reduced redox state, suggesting the treatment’s potential protective effects against oxidative stress and for the preservation of cellular function. Together, these data indicate the beneficial, tissue-specific effects of yerba maté supplementation on mitochondrial bioenergetics and redox states in healthy mice that are protective against obesity. Full article

(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)

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11 pages, 915 KiB

Open AccessArticle

Plasminogen Activator Inhibitor-1 and Vitamin D Association in the Overweight and Obese Pediatric Population

by Giovina Di Felice, Annamaria D’Alessandro, Anna Pastore, Michela Mariani, Danilo Fintini, Alessia Aureli, Simona Pezzi, Anna Lisa Montemari, Beatrice Barbara Rocco, Andrea Borseti, Andrea Onetti Muda, Melania Manco and Ottavia Porzio

Nutrients 2023, 15(17), 3717; https://doi.org/10.3390/nu15173717 - 25 Aug 2023

Viewed by 786

Abstract

Background: Childhood overweight and obesity have been described by the World Health Organization as noncommunicable diseases and among the greatest public health threats since they have reached epidemic proportions. A child with obesity risks becoming an adult with obesity and developing metabolic and hemostatic disorders which are the basis for the development of coronary heart diseases. Recently, a number of clinical reports have demonstrated that both an increase in plasminogen activator inhibitor-1 (PAI-1) and a deficiency in 25OH-vitamin D3 (VD) are associated with an increase in thrombotic episodes. Methods: PAI-1 and VD levels were measured in 259 clinically overweight and obese children aged between 2 and 18 years enrolled in the Nutritional Education Program of the Bambino Gesù Children’s Hospital and Research Institute of Rome (Italy) and 80 normal-weight subjects. Results: We observed increased HOMA-IR, PAI-1, and other inflammation indices associated with decreased VD levels when compared to normal-weight children. Conclusions: Our results demonstrated that overweight and obesity are correlated with higher levels of the inflammation index. Moreover, our patients show high PAI-1 and low VD levels, confirming the high thrombotic risk in our pediatric population. Full article

(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)

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14 pages, 9615 KiB

Open AccessArticle

Protection of Inonotus hispidus (Bull.) P. Karst. against Chronic Alcohol-Induced Liver Injury in Mice via Its Relieving Inflammation Response

by Xinghui Jin, Zhige Li, Yongfeng Zhang, Yanfeng Zhu, Ling Su, Jiyu Song, Jie Hao and Di Wang

Nutrients 2023, 15(16), 3530; https://doi.org/10.3390/nu15163530 - 10 Aug 2023

Viewed by 1238

Abstract

Alcoholic liver disease (ALD) can be induced by excessive alcohol consumption, and has a worldwide age-standardized incidence rate (ASIR) of approximately 5.243%. Inonotus hispidus (Bull.) P. Karst. (IH) is a mushroom with pharmacological effects. In ALD mice, the hepatoprotective effects of IH were investigated. IH strongly ameliorated alcohol-induced pathological changes in the liver, including liver structures and its function-related indices. Intestinal microbiota and serum metabolomics analysis showed that IH altered the associated anti-inflammatory microbiota and metabolites. According to results obtained from Western blot, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA), IH downregulated the levels of pro-inflammation factors interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), enhanced the expressions of peroxisome proliferator-activated receptor alpha (PPARα) and 15-hydroxprostaglandin dehydrogenase (15-PGDH), and inhibited the phosphorylated activation of Janus kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3, confirming the hepatoprotection of IH against alcohol damage via anti-inflammation. This study provides the experimental evidence for the hepatoprotective effects of IH in chronic ALD. Full article

(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)

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14 pages, 1202 KiB

Open AccessArticle

Dietary Fatty Acids Contribute to Maintaining the Balance between Pro-Inflammatory and Anti-Inflammatory Responses during Pregnancy

by Valeria Policastro, Dario Righelli, Lucilla Ravà, Pamela Vernocchi, Marzia Bianchi, Cristina Vallone, Fabrizio Signore and Melania Manco

Nutrients 2023, 15(11), 2432; https://doi.org/10.3390/nu15112432 - 23 May 2023

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Abstract

Background: During pregnancy, the balance between pro-inflammatory and anti-inflammatory responses is essential for ensuring healthy outcomes. Dietary Fatty acids may modulate inflammation. Methods: We investigated the association between dietary fatty acids as profiled on red blood cells membranes and a few pro- and anti-inflammatory cytokines, including the adipokines leptin and adiponectin at ~38 weeks in 250 healthy women. Results: We found a number of associations, including, but not limited to those of adiponectin with C22:3/C22:4 (coeff −1.44; p = 0.008), C18:1 c13/c14 (coeff 1.4; p = 0.02); endotoxin with C20:1 (coeff −0.9; p = 0.03), C22:0 (coeff −0.4; p = 0.05); MCP-1 with C16:0 (coeff 0.8; p = 0.04); and ICAM-1 with C14:0 (coeff −86.8; p = 0.045). Several cytokines including leptin were associated with maternal body weight (coeff 0.9; p = 2.31 × 10⁻⁵), smoking habits (i.e., ICAM-1 coeff 133.3; p = 0.09), or gestational diabetes (i.e., ICAM-1 coeff 688; p = 0.06). Conclusions: In a general cohort of pregnant women, the intake of fatty acids influenced the balance between pro- and anti-inflammatory molecules together with weight gain, smoking habits, and gestational diabetes. Full article

(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)

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11 pages, 564 KiB

Open AccessArticle

Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity

by Álvaro González-Domínguez, María Millán-Martínez, Jesús Domínguez-Riscart, Alfonso María Lechuga-Sancho and Raúl González-Domínguez

Nutrients 2023, 15(10), 2347; https://doi.org/10.3390/nu15102347 - 17 May 2023

Cited by 4 | Viewed by 1266

Abstract

Background: Trace elements and heavy metals have proven pivotal roles in childhood obesity and insulin resistance. However, growing evidence suggests that insulin resistance could encompass distinct phenotypic subtypes. Methods: Herein, we performed a comprehensive metallomics characterization of plasma samples from children and adolescents with obesity and concomitant insulin resistance, who were stratified as early (N = 17, 11.4 ± 2.4 years), middle (N = 16, 11.8 ± 1.9 years), and late (N = 33, 11.7 ± 2.0 years) responders according to the insulin secretion profile in response to an oral glucose tolerance test. To this end, we employed a high-throughput method aimed at determining the biodistribution of various essential and toxic elements by analyzing total metal contents, metal-containing proteins, and labile metal species. Results: Compared with the early responders, participants with delayed glucose-induced hyperinsulinemia showed a worsened insulin resistance (HOMA-IR, 4.5 vs. 3.8) and lipid profile (total cholesterol, 160 vs. 144 mg/dL; LDL-cholesterol, 99 vs. 82 mg/dL), which in turn was accompanied by sharpened disturbances in the levels of plasmatic proteins containing chromium (4.8 vs. 5.1 µg/L), cobalt (0.79 vs. 1.2 µg/L), lead (0.021 vs. 0.025 µg/L), and arsenic (0.077 vs. 0.17 µg/L). A correlation analysis demonstrated a close inter-relationship among these multielemental perturbations and the characteristic metabolic complications occurring in childhood obesity, namely impaired insulin-mediated metabolism of carbohydrates and lipids. Conclusions: These findings highlight the crucial involvement that altered metal homeostasis and exposure may have in regulating insulin signaling, glucose metabolism, and dyslipidemia in childhood obesity. Full article

(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)

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17 pages, 4858 KiB

Open AccessArticle

Artepillin C Time−Dependently Alleviates Metabolic Syndrome in Obese Mice by Regulating CREB/CRTC2−BMAL1 Signaling

by Lei Wang, Lingqin Zhou, Shuai Liu, Yaxin Liu, Jia Zhao, Yaqiong Chen and Yi Liu

Nutrients 2023, 15(7), 1644; https://doi.org/10.3390/nu15071644 - 28 Mar 2023

Cited by 2 | Viewed by 1495

Abstract

Artepillin C (APC), a cAMP-response element−binding (CREB)/CREB regulated transcription coactivator 2 (CRTC2) inhibitor isolated from Brazilian green propolis, can ameliorate metabolic syndrome in obese mice. Because the sensitivity and responsiveness of the body to the drug depend on the time of day and the circadian clock alignment, the optimal administration time of APC for desired efficacy in treating metabolic syndrome remains unclear. In this study, APC (20 mg/kg) or the vehicle was intraperitoneally injected into obese mice once daily for one or three weeks. The results of the insulin tolerance test, pyruvate tolerance test, and histological and biochemical assays showed that APC could improve whole−body glucose homeostasis and decrease hepatic lipid synthesis following a circadian rhythm. Further exploration of the underlying mechanism revealed that APC may disturb the diurnal oscillations of the expression of brain and muscle ARNT−like protein (BMAL1) in primary hepatocytes and the livers of the study subjects. Moreover, APC could inhibit hepatic BMAL1 expression by blocking the CREB/CRTC2 transcription complex. BMAL1 overexpression in primary hepatocytes or the livers of db/db mice antagonized the inhibitory effect of APC on hepatic lipid metabolism. In conclusion, the chronotherapy of APC may relieve metabolic syndrome in obese mice, and the mechanism behind APC−mediated time−of−day effects on metabolic syndrome were unveiled, thereby providing a foundation for optimized APC treatment from a mechanistic perspective. Full article

(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)

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18 pages, 10162 KiB

Open AccessArticle

Naringin Alleviates Glucose-Induced Aging by Reducing Fat Accumulation and Promoting Autophagy in Caenorhabditis elegans

by Peisen Guo, Panpan Wang, Limin Liu, Peixi Wang, Guimiao Lin, Zhi Qu, Zengli Yu and Nan Liu

Nutrients 2023, 15(4), 907; https://doi.org/10.3390/nu15040907 - 10 Feb 2023

Cited by 5 | Viewed by 2438

Abstract

Naringin (Nar) is a dihydroflavonoid compound, widely found in citrus fruit and used in Chinese herbal medicine. As a phytochemical, it acts as a dietary supplement that can delay aging and prevent aging-related disease, such as obesity and diabetes. However, its exact mechanism remains unclear. In this study, the high-glucose-induced (HGI) Caenorhabditis elegans model was used to evaluate the anti-aging and anti-obesity effects of Nar. The mean lifespan and fast movement span of HGI worms were extended roughly 24% and 11%, respectively, by Nar treatment. Oil red O staining revealed a significant reduction in fat accumulation and dFP::LGG-labeled worms showed the promotion of autophagy. Additionally, whole transcriptome sequencing and gene set variation analysis suggested that Nar upregulated the lipid biosynthesis and metabolism pathways, as well as the TGF-β, Wnt and longevity signaling pathways. Protein–protein interaction (PPI) network analysis identified hub genes in these pathways for further analysis. Mutant worms and RNA interference were used to study mechanisms; the suppression of hlh-30, lgg-1, unc-51, pha-4, skn-1 and yap-1 disabled the fat-lowering, lifespan-prolonging, and health-promoting properties of Nar. Collectively, our findings indicate that Nar plays an important role in alleviating HGI-aging and anti-obesity effects by reducing fat accumulation and promoting autophagy. Full article

(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)

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18 pages, 338 KiB

Open AccessArticle

Halting the Metabolic Complications of Antipsychotic Medication in Patients with a First Episode of Psychosis: How Far Can We Go with the Mediterranean Diet? A Pilot Study

by Savina Ntalkitsi, Dimitris Efthymiou, Vasilios Bozikas and Emilia Vassilopoulou

Nutrients 2022, 14(23), 5012; https://doi.org/10.3390/nu14235012 - 25 Nov 2022

Cited by 2 | Viewed by 2180

Abstract

Patients with first-episode psychosis (FEP) often adopt unhealthy dietary patterns, with a risk of weight gain and metabolic and cardiovascular disease. In 21 FEP patients receiving nutritional intervention based on the Mediterranean diet (MedDiet), we explored differences in anthropometric and biometric parameters, according to their antipsychotic (AP) medication: AP1, associated with a lower risk, or AP2, associated with a higher risk of weight gain and metabolic complications. The blood biochemical profile was recorded before and after dietary intervention, and dietary habits and body composition were monitored for six months. Following intervention, all of the patients recorded significant increases in the consumption of fruit and vegetables and decreases in red meat and poultry consumption, with closer adherence to the MedDiet and a reduction in the daily intake of calories, carbohydrates, and sodium. Vegetable consumption and energy, protein, and carbohydrate intake were lower in AP1 patients than in AP2 patients. There was no significant weight gain overall. A reduction was demonstrated in total and LDL cholesterol, sodium, urea, and iron (lower in AP1 patients). It was evident that AP medication affected blood levels of lipids, urea, and iron of FEP patients, but MedDiet nutritional intervention led to a significant improvement in their eating habits, with a restriction in weight gain and a decrease in blood sodium and urea. Full article

(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)

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15 pages, 659 KiB

Open AccessReview

The Role of Epigenetic Control of Mitochondrial (Dys)Function in MASLD Onset and Progression

by Valerio Caputo, Giovanni Tarantino, Silvano Junior Santini, Giovanna Fracassi and Clara Balsano

Nutrients 2023, 15(22), 4757; https://doi.org/10.3390/nu15224757 - 12 Nov 2023

Cited by 3 | Viewed by 1388

Abstract

Metabolic dysfunction-associated steatotic fatty liver disease (MASLD), a novel definition for NAFLD, represents one of the most common causes of liver disease, and its incidence is increasing worldwide. It is characterized by a complex etiopathogenesis in which mitochondrial dysfunction exerts a pivotal role together with alteration of lipid metabolism, inflammation, and oxidative stress. Nutrients and bioactive compounds can influence such mechanisms so that changes in diet and lifestyle are regarded as important treatment strategies. Notably, natural compounds can exert their influence through changes of the epigenetic landscape, overall resulting in rewiring of molecular networks involved in cell and tissue homeostasis. Considering such information, the present review aims at providing evidence of epigenetic modifications occurring at mitochondria in response to natural and bioactive compounds in the context of liver (dys)function. For this purpose, recent studies reporting effects of compounds on mitochondria in the context of NAFLD/MASLD, as well as research showing alteration of DNA methylation and non-coding RNAs-related circuits occurring at liver mitochondria, will be illustrated. Overall, the present review will highlight the importance of understanding the bioactive compounds-dependent epigenetic modulation of mitochondria for improving the knowledge of MASLD and identifying biomarkers to be employed for effective preventative strategies or treatment protocols. Full article

(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)

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