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Diet, Liver, Oxidative Stress and Metabolic Syndrome

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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 (31 May 2021) | Viewed by 51920

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Special Issue Editors

Dr. Christina Chrysohoou

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Guest Editor

First Cardiology Department, Hippokration General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Interests: heart failure; cardiovascular epidemiology; cardiovascular imaging
Special Issues, Collections and Topics in MDPI journals

Prof. Konstantinos Tsioufis

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Guest Editor

National and Kapodistrian University of Athens, Athens, Greece
Interests: arterial hypertension; cardiometabolics; invasive cardiology

Special Issue Information

Dear Colleagues,

This Special Issue “Diet, Liver, Oxidative Stress and Metabolic Syndrome” should shed light on the association between various nutritional aspects—on the basis of nutrients, dietary patterns (defined a priori or a posteriori) with anti-inflammatory and antioxidant capacity or dietary behaviors—and liver health.

The prevalence of liver steatosis and fibrosis, principally under the umbrella of non-alcoholic fatty liver disease (NAFLD), is increasing in parallel with the rising rates of obesity, diabetes and metabolic syndrome. All these metabolic abnormalities seem to share common mechanisms related to inflammation and oxidative stress. NAFLD demonstrates a key role in metabolic abnormalities related to excess adiposity, while it is increasingly suggested as a precursor of metabolic syndrome. To this issue, NAFLD has been proposed to be included in the definition of metabolic syndrome. The early identification and management of NAFLD contributes to the early prevention and treatment of not only steatohepatitis (NASH) but also major chronic diseases such as cardiovascular disease and new-onset diabetes mellitus, which are the main causes of morbidity and mortality among subjects with NAFLD.

No specific pharmaceutical plan exists for the treatment of NAFLD and the accompanying metabolic syndrome-related comorbidities. Lifestyle interventions are strongly recommended, focusing on hypocaloric diets to achieve weight loss, or, most recently, plant-based diets and a Mediterranean dietary pattern are highly discussed as efficient preventive measures.

In conclusion, this Special Issue should review all aspects concerning effective nutrition-related plans in this field as well as the underlying mechanisms behind them in order to improve the primary prevention strategies for these metabolic disorders.

Dr. Christina Chrysohoou
Prof. Konstantinos Tsioufis
Guest Editors

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Keywords

liver steatosis
liver fibrosis
non-alcoholic fatty liver disease
metabolic syndrome
diabetes
nutrition
dietary patterns
plant-based diets
Mediterranean diet
weight management
oxidative stress
inflammation
insulin resistance
primary prevention
disease progression

Published Papers (10 papers)

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Research

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11 pages, 286 KiB

Open AccessFeature PaperArticle

The Homocysteine and Metabolic Syndrome: A Mendelian Randomization Study

by Ho-Sun Lee, Sanghwan In and Taesung Park

Nutrients 2021, 13(7), 2440; https://doi.org/10.3390/nu13072440 - 16 Jul 2021

Cited by 11 | Viewed by 4229

Abstract

Homocysteine (Hcy) is well known to be increased in the metabolic syndrome (MetS) incidence. However, it remains unclear whether the relationship is causal or not. Recently, Mendelian Randomization (MR) has been popularly used to assess the causal influence. In this study, we adopted MR to investigate the causal influence of Hcy on MetS in adults using three independent cohorts. We considered one-sample MR and two-sample MR. We analyzed one-sample MR in 5902 individuals (2090 MetS cases and 3812 controls) from the KARE and two-sample MR from the HEXA (676 cases and 3017 controls) and CAVAS (1052 cases and 764 controls) datasets to evaluate whether genetically increased Hcy level influences the risk of MetS. In observation studies, the odds of MetS increased with higher Hcy concentrations (odds ratio (OR) 1.17, 95%CI 1.12–1.22, p < 0.01). One-sample MR was performed using two-stage least-squares regression, with an MTHFR C677T and weighted Hcy generic risk score as an instrument. Two-sample MR was performed with five genetic variants (rs12567136, rs1801133, rs2336377, rs1624230, and rs1836883) by GWAS data as the instrumental variables. For sensitivity analysis, weighted median and MR–Egger regression were used. Using one-sample MR, we found an increased risk of MetS (OR 2.07 per 1-SD Hcy increase). Two-sample MR supported that increased Hcy was significantly associated with increased MetS risk by using the inverse variance weighted (IVW) method (beta 0.723, SE 0.119, and p < 0.001), the weighted median regression method (beta 0.734, SE 0.097, and p < 0.001), and the MR–Egger method (beta 2.073, SE 0.843, and p = 0.014) in meta-analysis. The MR–Egger slope showed no evidence of pleiotropic effects (intercept −0.097, p = 0.107). In conclusion, this study represented the MR approach and elucidates the significant relationship between Hcy and the risk of MetS in the Korean population. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

16 pages, 3495 KiB

Open AccessArticle

Lipoic Acid Exacerbates Oxidative Stress and Lipid Accumulation in the Liver of Wistar Rats Fed a Hypercaloric Choline-Deficient Diet

by Lidia V. Kravchenko, Ilya V. Aksenov, Nikolay S. Nikitin, Galina V. Guseva, Ludmila I. Avrenyeva, Nikita V. Trusov, Anastasia S. Balakina and Victor A. Tutelyan

Nutrients 2021, 13(6), 1999; https://doi.org/10.3390/nu13061999 - 10 Jun 2021

Cited by 3 | Viewed by 2502

Abstract

Non-alcoholic fatty liver disease (NAFLD) is currently estimated as the most prevalent chronic liver disease in all age groups. An increasing body of evidence obtained in experimental and clinical data indicates that oxidative stress is the most important pathogenic factor in the development of NAFLD. The study aimed to investigate the impact of α-lipoic acid (LA), widely used as an antioxidant, on the effects of a hypercaloric choline-deficient diet. Male Wistar rats were divided into three groups: control diet (C); hypercaloric choline-deficient diet (HCCD), and hypercaloric choline-deficient diet with α-lipoic acid (HCCD+LA). Supplementation of HCCD with LA for eight weeks led to a decrease in visceral adipose tissue/body weight ratio, the activity of liver glutathione peroxidase and paraoxonase-1, plasma, and liver total antioxidant activity, as well as an increase in liver/body weight ratio, liver total lipid and triglyceride content, and liver transaminase activities compared to the HCCD group without LA. In conclusion, our study shows that α-lipoic acid detains obesity development but exacerbates the severity of diet-induced oxidative stress and lipid accumulation in the liver of male Wistar rats fed a hypercaloric choline-deficient diet. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

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17 pages, 3727 KiB

Open AccessArticle

Prolonged Changes in Hepatic Mitochondrial Activity and Insulin Sensitivity by High Fructose Intake in Adolescent Rats

by Arianna Mazzoli, Cristina Gatto, Raffaella Crescenzo, Luisa Cigliano and Susanna Iossa

Nutrients 2021, 13(4), 1370; https://doi.org/10.3390/nu13041370 - 19 Apr 2021

Cited by 7 | Viewed by 2672

Abstract

Persistence of damage induced by unhealthy diets during youth has been little addressed. Therefore, we investigated the impact of a short-term fructose-rich diet on liver metabolic activity in adolescent rats and the putative persistence of alterations after removing fructose from the diet. Adolescent rats were fed a fructose-rich diet for three weeks and then switched to a control diet for further three weeks. Body composition and energy balance were not affected by fructose-rich diet, while increased body lipids and lipid gain were found after the rescue period. Switching to a control diet reversed the upregulation of plasma fructose, uric acid, lipocalin, and haptoglobin, while plasma triglycerides, alanine aminotransferase, lipopolysaccharide, and tumor necrosis factor alpha remained higher. Hepatic steatosis and ceramide were increased by fructose-rich diet, but reversed by returning to a control diet, while altered hepatic response to insulin persisted. Liver fatty acid synthase and stearoyl-CoA desaturase (SCD) activities were upregulated by fructose-rich diet, and SCD activity remained higher after returning to the control diet. Fructose-induced upregulation of complex II-driven mitochondrial respiration, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, and peroxisome proliferator activated receptor α also persisted after switching to control diet. In conclusion, our results show prolonged fructose-induced dysregulation of liver metabolic activity. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

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14 pages, 1530 KiB

Open AccessArticle

Fructo-Oligosaccharides and Pectins Enhance Beneficial Effects of Raspberry Polyphenols in Rats with Nonalcoholic Fatty Liver

by Bartosz Fotschki, Jerzy Juśkiewicz, Adam Jurgoński and Michał Sójka

Nutrients 2021, 13(3), 833; https://doi.org/10.3390/nu13030833 - 03 Mar 2021

Cited by 11 | Viewed by 3164

Abstract

In recent years, nonalcoholic fatty liver disorders have become one of the most common liver pathologies; therefore, it is necessary to investigate the dietary compounds that may support the regulation of liver metabolism and related inflammatory processes. The present study examines the effect of raspberry polyphenolic extract (RE) combined with fructo-oligosaccharides (FOSs) or pectins (PECs) on caecal microbial fermentation, liver lipid metabolism and inflammation in rats with fatty liver induced by an obesogenic diet. The combination of RE with FOSs or PECs reduced the production of short-chain fatty acids in the caecum. RE combined with FOSs exerted the most favourable effects on liver lipid metabolism by decreasing liver fat, cholesterol, triglyceride content and hepatic steatosis. RE and FOSs reduced lobular and portal inflammatory cell infiltration and IL-6 plasma levels. These effects might be related to a decrease in the hepatic expressions of PPARγ and ANGPTL4. In conclusion, PECs and FOSs enhanced the effects of RE against disorders related to nonalcoholic fatty liver; however, the most effective dietary treatment in the regulation of liver lipid metabolism and inflammation caused by an obesogenic diet was the combination of RE with FOSs. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

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17 pages, 2020 KiB

Open AccessArticle

Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors

by Christina Chrysohoou, Matina Kouvari, George Lazaros, John Varlas, Kyriakos Dimitriadis, Marina Zaromytidou, Constantina Masoura, John Skoumas, Manolis Kambaxis, Nikos Galiatsatos, Aggelos Papanikolaou, Panagiotis Xydis, Konstantinos Konstantinou, Christos Pitsavos, Konstantinos Tsioufis and Christodoulos Stefanadis

Nutrients 2020, 12(11), 3293; https://doi.org/10.3390/nu12113293 - 27 Oct 2020

Cited by 7 | Viewed by 2285

Abstract

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, n = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants >65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis; in age >65 years, Hazard Ratio (HR)_{(2nd vs. 1st SMI tertile)} = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR_{(2nd vs. 1st SMI tertile)} = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

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15 pages, 3173 KiB

Open AccessArticle

Endoplasmic Reticulum Stress Affects Cholesterol Homeostasis by Inhibiting LXRα Expression in Hepatocytes and Macrophages

by Tian Wang, Yiyang Zhao, Zhongsheng You, Xiatian Li, Mingdi Xiong, Hua Li and Nianlong Yan

Nutrients 2020, 12(10), 3088; https://doi.org/10.3390/nu12103088 - 11 Oct 2020

Cited by 23 | Viewed by 3146

Abstract

Atherosclerosis (AS) is the most common cardiovascular disease, and reverse cholesterol transport (RCT) plays an important role in maintaining cholesterol homeostasis. Both endoplasmic reticulum (ER) stress and LXRα can affect the metabolism of cholesterol. However, whether ER stress can modulate cholesterol metabolism by LXRα in hepatocytes and macrophages remains unclear. Therefore, in this study, we aimed to explore the relationship between ER stress induced by tunicamycin and LXRα in hepatocytes and macrophages and clarify their possible mechanisms and roles in AS. C57BL/6 mice and Huh-7 and THP-1 cells were treated with tunicamycin and LXR-623 (an agonist of LXRα) alone or in combination. Tunicamycin-induced ER stress caused liver injury; promoted the accumulation of cholesterol and triglycerides; inhibited the expression of LXRα, ABCA1 and ABCG1 in the livers of mice, thus reducing serum high-density lipoprotein (HDL)-C, low-density lipoprotein (LDL)-C, total cholesterol and triglyceride levels; however, LXR-623 could attenuate ER stress and reverse these changes. We also obtained the same results in Huh-7 and THP-1 cells. ER stress induced by tunicamycin could clearly be reversed by activating LXRα because it promoted cholesterol efflux by enhancing the expression of ABCA1 and ABCG1 in hepatocytes and macrophages, contributing to attenuation of the development of AS. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

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16 pages, 801 KiB

Open AccessArticle

Sea Buckthorn and Rosehip Oils with Chokeberry Extract to Prevent Hypercholesterolemia in Mice Caused by a High-Fat Diet In Vivo

by Lubov Tereshchuk, Kseniya Starovoytova, Olga Babich, Lyubov Dyshlyuk, Irina Sergeeva, Valery Pavsky, Svetlana Ivanova and Alexander Prosekov

Nutrients 2020, 12(10), 2941; https://doi.org/10.3390/nu12102941 - 25 Sep 2020

Cited by 7 | Viewed by 3443

Abstract

Dietary supplementation based on sea buckthorn and rosehip oils with added chokeberry extract was studied. We added the dietary supplement to the feed mixtures for laboratory animals. The possible toxicological effects and hypocholesterolemic, hepatoprotective activity of the dietary supplement in vivo were studied. After the observation period (6 weeks), no significant changes were found in the mass of organs and blood serum of laboratory animals (p > 0.05). However, there was a decrease in hypercholesterolemic indicators. Regular consumption of sea buckthorn and rosehip oils with added chokeberry extract (dietary supplement “ESB-1”) by laboratory animals inhibited the activity of liver enzymes and increased the antioxidant activity of blood serum (after the subcutaneous injection of sunflower oil/oil solution of carbon tetrachloride) but was not sufficient to bring them to physiological standards. The hypocholesterolemic and antioxidant properties of our dietary supplement already allow us to consider it a component of functional food products or a dietary supplement base. However, the full range of its biologically active properties, including the hepatoprotective function and regulation of metabolic disorders, has not been studied yet, which sets the direction of further research in vivo models and clinical practice to confirm its effectiveness in humans. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

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21 pages, 991 KiB

Open AccessReview

Recent Developments in Rodent Models of High-Fructose Diet-Induced Metabolic Syndrome: A Systematic Review

by Alvin Man Lung Chan, Angela Min Hwei Ng, Mohd Heikal Mohd Yunus, Ruszymah Bt Hj Idrus, Jia Xian Law, Muhammad Dain Yazid, Kok-Yong Chin, Sharen Aini Shamsuddin and Yogeswaran Lokanathan

Nutrients 2021, 13(8), 2497; https://doi.org/10.3390/nu13082497 - 22 Jul 2021

Cited by 24 | Viewed by 4404

Abstract

Metabolic syndrome (MetS) is the physiological clustering of hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, and insulin resistance. The MetS-related chronic illnesses encompass obesity, the cardiovascular system, renal operation, hepatic function, oncology, and mortality. To perform pre-clinical research, it is imperative that these symptoms be successfully induced and optimized in lower taxonomy. Therefore, novel and future applications for a disease model, if proven valid, can be extrapolated to humans. MetS model establishment is evaluated based on the significance of selected test parameters, paradigm shifts from new discoveries, and the accessibility of the latest technology or advanced methodologies. Ultimately, the outcome of animal studies should be advantageous for human clinical trials and solidify their position in advanced medicine for clinicians to treat and adapt to serious or specific medical situations. Rodents (Rattus norvegicus and Mus musculus) have been ideal models for mammalian studies since the 18th century and have been mapped extensively. This review compiles and compares studies published in the past five years between the multitude of rodent comparative models. The response factors, niche parameters, and replicability of diet protocols are also compiled and analyzed to offer insight into MetS-related disease-specific modelling. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

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15 pages, 1888 KiB

Open AccessReview

Bee Pollen: Current Status and Therapeutic Potential

by Shaden A. M. Khalifa, Mohamed H. Elashal, Nermeen Yosri, Ming Du, Syed G. Musharraf, Lutfun Nahar, Satyajit D. Sarker, Zhiming Guo, Wei Cao, Xiaobo Zou, Aida A. Abd El-Wahed, Jianbo Xiao, Hany A. Omar, Mohamed-Elamir F. Hegazy and Hesham R. El-Seedi

Nutrients 2021, 13(6), 1876; https://doi.org/10.3390/nu13061876 - 31 May 2021

Cited by 78 | Viewed by 18048

Abstract

Bee pollen is a combination of plant pollen and honeybee secretions and nectar. The Bible and ancient Egyptian texts are documented proof of its use in public health. It is considered a gold mine of nutrition due to its active components that have significant health and medicinal properties. Bee pollen contains bioactive compounds including proteins, amino acids, lipids, carbohydrates, minerals, vitamins, and polyphenols. The vital components of bee pollen enhance different bodily functions and offer protection against many diseases. It is generally marketed as a functional food with affordable and inexpensive prices with promising future industrial potentials. This review highlights the dietary properties of bee pollen and its influence on human health, and its applications in the food industry. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

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28 pages, 6660 KiB

Open AccessSystematic Review

Positive Effects of Exercise Intervention without Weight Loss and Dietary Changes in NAFLD-Related Clinical Parameters: A Systematic Review and Meta-Analysis

by Ambrin Farizah Babu, Susanne Csader, Johnson Lok, Carlos Gómez-Gallego, Kati Hanhineva, Hani El-Nezami and Ursula Schwab

Nutrients 2021, 13(9), 3135; https://doi.org/10.3390/nu13093135 - 08 Sep 2021

Cited by 52 | Viewed by 6685

Abstract

One of the focuses of non-alcoholic fatty liver disease (NAFLD) treatment is exercise. Randomized controlled trials investigating the effects of exercise without dietary changes on NAFLD-related clinical parameters (liver parameters, lipid metabolism, glucose metabolism, gut microbiota, and metabolites) were screened using the PubMed, Scopus, Web of Science, and Cochrane databases on 13 February 2020. Meta-analyses were performed on 10 studies with 316 individuals who had NAFLD across three exercise regimens: aerobic exercise, resistance training, and a combination of both. No studies investigating the role of gut microbiota and exercise in NAFLD were found. A quality assessment via the (RoB)2 tool was conducted and potential publication bias, statistical outliers, and influential cases were identified. Overall, exercise without significant weight loss significantly reduced the intrahepatic lipid (IHL) content (SMD: −0.76, 95% CI: −1.04, −0.48) and concentrations of alanine aminotransaminase (ALT) (SMD: −0.52, 95% CI: −0.90, −0.14), aspartate aminotransaminase (AST) (SMD: −0.68, 95% CI: −1.21, −0.15), low-density lipoprotein cholesterol (SMD: −0.34, 95% CI: −0.66, −0.02), and triglycerides (TG) (SMD: −0.59, 95% CI: −1.16, −0.02). The concentrations of high-density lipoprotein cholesterol, total cholesterol (TC), fasting glucose, fasting insulin, and glycated hemoglobin were non-significantly altered. Aerobic exercise alone significantly reduced IHL, ALT, and AST; resistance training alone significantly reduced TC and TG; a combination of both exercise types significantly reduced IHL. To conclude, exercise overall likely had a beneficial effect on alleviating NAFLD without significant weight loss. The study was registered at PROSPERO: CRD42020221168 and funded by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 813781. Full article

(This article belongs to the Special Issue Diet, Liver, Oxidative Stress and Metabolic Syndrome)

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