Submit to Genes Review for Genes Propose a Special Issue

Journal Menu

Journal Browser

Genetic and Epigenetic Investigations into the Pathogenesis and Pathophysiology of the Metabolic Syndrome

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 22378

Share This Special Issue

Special Issue Editor

Dr. David Q-H Wang

E-Mail Website
Guest Editor

Albert Einstein College of Medicine, Bronx, NY 10461, USA
Interests: cholesterol and bile acid metabolism in the liver; bile; intestine; plasma; cholelithiasis; intestinal lipid absorption; nonalcoholic fatty liver disease; alcoholic liver disease; cholestasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic syndrome is defined as a clustering of metabolic abnormalities that include central obesity, insulin resistance, hypertriglyceridemia, hypertriglyceridemia, hypertension, and reduced high-density lipoprotein cholesterol concentrations. It is also associated with other comorbidities including the proinflammatory state, prothrombotic state, nonalcoholic fatty liver disease, cholesterol gallstone disease, and reproductive disorders. The metabolic syndrome is one of the risk factors for the epidemic of type 2 diabetes and cardiovascular disease in the 21st century because it appears as a worldwide epidemic and major public health concern with a high prevalence rate not only in the USA and Europe, but also in most Asian and South American countries. It has been found that the metabolic syndrome is associated with a significant increase in cardiovascular disease and type 2 diabetes. Although it is unclear whether there is a unifying pathogenic mechanism that could elucidate the pathophysiology of the metabolic syndrome, abdominal obesity and insulin resistance definitively play a pivotal role in triggering the development of the metabolic syndrome. Because the metabolic syndrome could be caused largely by an inactive lifestyle, overconsumption of food, and the resulting abdominal obesity, it is strongly recommended that lifestyle changes and weight loss are the first step to prevent or treat metabolic syndrome. In addition, other cardiac risk factors should be actively managed in individuals with metabolic syndrome.

In this Special Issue, topics will be focused on genetic and epigenetic investigations into the pathogenesis and pathophysiology of the metabolic syndrome, as well as epidemiology and natural course of this metabolic disorder. In addition, special emphasis will be given to the abnormal genetic, cellular, and molecular mechanisms underlying the dysfunctional lipid and glucose metabolism as risk factors for the development of metabolic syndrome.

This Special Issue is also dedicated to the cellular and molecular mechanisms of the pathophysiology of risk components for the development of the metabolic syndrome, such as obesity, diabetes, insulin resistance, hypertriglyceridemia, hypertriglyceridemia, hypertension, cardiovascular disease, gallstones, nonalcoholic fatty liver disease, and abnormal lipoprotein metabolism. Taken together, basic, translational, and clinical studies on these topics are strongly recommended for publication in this Special Issue.

We cordially invite all researchers, scientists, investigators, and clinicians who work in these fields to submit their manuscripts (i.e., original research papers, review articles and commentaries) for publication in this Special Issue of Genes.

Dr. David Q-H Wang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

metabolic disorder
obesity
diabetes
hypertension
nonalcoholic fatty liver disease
genetic disorders
gene mutation and variants
single cell genetics
next-generation sequencing and genome analysis
epigenetics

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (7 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

16 pages, 924 KiB

Open AccessEditor’s ChoiceArticle

Association between SNPs in Leptin Pathway Genes and Anthropometric, Biochemical, and Dietary Markers Related to Obesity

by Ricardo Omar Cadena-López, Lourdes Vanessa Hernández-Rodríguez, Adriana Aguilar-Galarza, Willebaldo García-Muñoz, Lorenza Haddad-Talancón, Ma. de Lourdes Anzures-Cortes, Claudia Velázquez-Sánchez, Karla Lucero Flores-Viveros, Miriam Aracely Anaya-Loyola, Teresa García-Gasca, Víctor Manuel Rodríguez-García and Ulisses Moreno-Celis

Genes 2022, 13(6), 945; https://doi.org/10.3390/genes13060945 - 25 May 2022

Cited by 6 | Viewed by 4207

Abstract

Obesity is one of the main public health problems in Mexico and the world and one from which a large number of pathologies derive. Single nucleotide polymorphisms (SNPs) of various genes have been studied and proven to contribute to the development of multiple diseases. SNPs of the leptin pathway have been associated with the control of hunger and energy expenditure as well as with obesity and type 2 diabetes mellitus. Therefore, the present work focused on determining the association between anthropometric markers and biochemical and dietary factors related to obesity and SNPs of leptin pathway genes, such as the leptin gene (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), and the melanocortin 4 receptor (MC4R). A population of 574 young Mexican adults of both sexes, aged 19 years old on average and without metabolic disorders previously diagnosed, underwent a complete medical and nutritional evaluation, biochemical determination, and DNA extraction from the blood; DNA samples were subsequently genotyped. Association analyses between anthropometric, biochemical, and dietary variables with SNPs were performed using binary logistic regressions (p-value = 0.05). Although the sampled population did not have previously diagnosed diseases, the evaluation results showed that 33% were overweight or obese according to BMI and 64% had non-clinically elevated levels of body fat. From the 74 SNP markers analyzed from the five previously mentioned genes, 62 showed polymorphisms within the sampled population, and only 35 of these had significant associations with clinical variables. The risk associations (OR > 1) occurred between clinical markers with elevated values for waist circumference, waist–height index, BMI, body fat percentage, glucose levels, insulin levels, HOMA-IR, triglyceride levels, cholesterol levels, LDL-c, low HDL-c, carbohydrate intake, and protein intake and SNPs of the LEP, LEPR, PCSK1, and MC4R genes. On the other hand, the protective associations (OR < 1) were associated with markers including elevated values for insulin, HOMA-IR, cholesterol, c-LDL, energy intake > 2440 Kcal/day, and lipid intake and SNPs of the LEP and LEPR genes and POMC. The present study describes associations between SNPs in leptin pathway genes, revealing positive and negative interactions between reported SNPs and the clinical markers related to obesity in a sampled Mexican population. Hence, our results open the door for the further study of new genetic variants and their influence on obesity. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Investigations into the Pathogenesis and Pathophysiology of the Metabolic Syndrome)

► Show Figures

Figure 1

10 pages, 274 KiB

Open AccessEditor’s ChoiceArticle

Gene Polymorphisms of Hormonal Regulators of Metabolism in Patients with Schizophrenia with Metabolic Syndrome

by Anastasiia S. Boiko, Ivan V. Pozhidaev, Diana Z. Paderina, Irina A. Mednova, Anastasya A. Goncharova, Olga Yu. Fedorenko, Elena G. Kornetova, Arkadiy V. Semke, Nikolay A. Bokhan, Anton J. M. Loonen and Svetlana A. Ivanova

Genes 2022, 13(5), 844; https://doi.org/10.3390/genes13050844 - 8 May 2022

Cited by 4 | Viewed by 2327

Abstract

Background: Metabolic syndrome (MetS) is a common complication of long-term treatment of persons with schizophrenia taking (atypical) antipsychotics. In this study, we investigated the existence of an association with polymorphisms of genes for four hormones that regulate energy metabolism. Methods: We recruited 517 clinically admitted white patients (269M/248F) with a verified diagnosis of schizophrenia (ICD-10) and with a stable physical condition. Participants were classified for having or not having MetS and genotyped for 20 single-nucleotide polymorphisms (SNPs) in the genes encoding insulin-induced gene 2 (INSIG2), ghrelin (GHRL), leptin (LEP), and leptin receptor (LEPR). Results: The 139 patients (26.9%) with MetS were significantly more likely to be women, older, and ill longer, and had a larger body mass index (BMI). Four polymorphisms (rs10490624, rs17587100, rs9308762, and rs10490816) did not meet the Hardy–Weinberg equilibrium (HWE) criterion and were excluded. Only genotypes and alleles of the rs3828942 of LEP gene (chi2 = 7.665, p = 0.022; chi2 = 5.136, p = 0.023) and the genotypes of the rs17047718 of INSIG2 gene (chi2 = 7.7, p = 0.021) had a significant association with MetS. Conclusions: The results of our study suggest that the LEP and INSIG2 genes play a certain causal role in the development of MetS in patients with schizophrenia. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Investigations into the Pathogenesis and Pathophysiology of the Metabolic Syndrome)

12 pages, 4758 KiB

Open AccessArticle

The Preliminary Evaluation of Epigenetic Modifications Regulating the Expression of IL10 in Insulin-Resistant Adipocytes

by Aneta Cierzniak, Krzysztof Kaliszewski and Małgorzata Małodobra-Mazur

Genes 2022, 13(2), 294; https://doi.org/10.3390/genes13020294 - 2 Feb 2022

Cited by 2 | Viewed by 2135

Abstract

A higher level of IL10 expression in obesity and insulin resistance was observed in both human and mouse WAT. In our research, we analyzed the influence of insulin resistance on epigenetic modification within the promoter region IL10 gene and the potential influence of these modifications on its expression. Studies were performed using two cell models for the analysis: human, preadipocytes derived from adipose (visceral and subcutaneous) tissues and murine 3T3-L1 fibroblasts. We demonstrated a significant increase in the IL10 expression level, IL10 promoter region methylation, and histone 3 epigenetic modifications: H3K4me and H3K9/14ac, in insulin resistance cells (IR) from SAT cell culture. In IR cells from VAT cell culture, we observed decreased IL10 expression with a simultaneous increase of IL10 promoter region methylation. In IR cells from 3T3L1 cell culture, we observed the increased expression of IL10 as well as the decreased levels of methylation in the IL10 promoter region and histone methylation (H3K4me) and acetylation (H3K9/14ac). The presented analyses suggest a potential impact of epigenetic modifications on gene expression and a potential mutual influence of epigenetic modifications on each other or the activation of specific epigenetic regulation at a different stage of the development of insulin resistance in cells. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Investigations into the Pathogenesis and Pathophysiology of the Metabolic Syndrome)

► Show Figures

Figure 1

13 pages, 1529 KiB

Open AccessArticle

Impact of Sequential Lipid Meals on Lymphatic Lipid Absorption and Transport in Rats

by Qi Zhu, Qing Yang, Ling Shen, Jie Qu, Meifeng Xu, David Q.-H. Wang, Patrick Tso and Min Liu

Genes 2022, 13(2), 277; https://doi.org/10.3390/genes13020277 - 30 Jan 2022

Cited by 1 | Viewed by 2782

Abstract

The sequential meal pattern has recently received more attention because it reflects a phycological diet style for human beings. The present study investigated the effects of the second lipid meal on lymphatic lipid absorption and transport in adult rats following a previous lipid meal. Using the well-established lymph fistula model, we found that the second lipid meal significantly increased the lymphatic output of triglycerides, cholesterol, phospholipids, and non-esterified fatty acids compared with a single lipid meal. Besides that, the time reaching the peak of each lipid output was significantly faster compared with the first lipid meal. Additionally, the second lipid meal significantly increased the lymphatic output of apolipoprotein A-IV (ApoA-IV), but not apolipoprotein B-48 (ApoB-48) or apolipoprotein A-I (ApoA-I). Interestingly, the triglyceride/apoB-48 ratio was significantly increased after the second lipid meal, indicating the increased chylomicron size in the lymph. Finally, the second lipid meal increased the lymphatic output of rat mucosal mast cell protease II (RMCPII). No change was found in the expression of genes related to the permeability of lymphatic lacteals, including vascular endothelial growth factor-A (Vegfa), vascular endothelial growth factor receptor 1 (Flt1), and Neuropilin1 (Nrp1). Collectively, the second lipid meal led to the rapid appearance of bigger-sized chylomicrons in the lymph. It also increased the lymphatic output of various lipids and apoA-IV, and mucosal mast cell activity in the intestine. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Investigations into the Pathogenesis and Pathophysiology of the Metabolic Syndrome)

► Show Figures

Figure 1

8 pages, 1065 KiB

Open AccessArticle

Adiponectin Gene Polymorphism (rs17300539) Has No Influence on the Occurrence of Metabolic Syndrome in Women with Polycystic Ovary Syndrome

by Izabela Nowak, Sylwester Ciećwież, Beata Łój, Jacek Brodowski and Agnieszka Brodowska

Genes 2021, 12(12), 1902; https://doi.org/10.3390/genes12121902 - 27 Nov 2021

Cited by 3 | Viewed by 2005

Abstract

Adiponectin (rs17300539) is implicated in the pathogenesis of metabolic syndrome (MS), a common comorbidity of polycystic ovarian syndrome (PCOS). The aim of this study was to analyze the association between adiponectin gene polymorphism and incidence of MS in patients with PCOS. The study included 201 women (age 18 to 35 years), among them 81 patients with PCOS without concomitant MS, 70 subjects with PCOS and concomitant, and 50 regularly menstruating controls. Adiponectin gene polymorphism (11391 G/A, rs17300539) was determined by means of a real-time PCR. The study groups did not differ significantly in terms of their age and frequencies of various genotypes of the adiponectin gene polymorphism. The largest proportion in the whole group was Caucasian women (n = 178, 88.56%), who carried the GG genotype of the polymorphism; frequencies of GA and AA genotypes in the whole study group were 10.94% (n = 22) and 0.5% (n = 1), respectively. The presence of G or A allele of the rs17300539 adiponectin gene polymorphism was not associated with a greater likelihood of PCOS with/without concomitant MS. The hereby presented findings imply that MS is a common comorbidity in women with PCOS. However, the incidence of concomitant MS does not seem to be associated with adiponectin gene polymorphism. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Investigations into the Pathogenesis and Pathophysiology of the Metabolic Syndrome)

► Show Figures

Figure 1

13 pages, 7461 KiB

Open AccessArticle

Heterozygous Nme7 Mutation Affects Glucose Tolerance in Male Rats

by Lucie Šedová, Jan Prochazka, Dagmar Zudová, Běla Bendlová, Josef Včelák, Radislav Sedlacek and Ondřej Šeda

Genes 2021, 12(7), 1087; https://doi.org/10.3390/genes12071087 - 18 Jul 2021

Cited by 7 | Viewed by 3179

Abstract

Complex metabolic conditions such as type 2 diabetes and obesity result from the interaction of numerous genetic and environmental factors. While the family of Nme proteins has been connected so far mostly to development, proliferation, or ciliary functions, several lines of evidence from human and experimental studies point to the potential involvement of one of its members, NME7 (non-metastatic cells 7, nucleoside diphosphate kinase 7) in carbohydrate and lipid metabolism. As a complete lack of Nme7 is semilethal in rats, we compared morphometric, metabolic, and transcriptomic profiles of standard diet-fed heterozygous Nme7+/− on male rats vs. their wild-type Nme7+/+ controls. Nme7+/− animals showed increased body weight, adiposity, higher insulin levels together with decreased glucose tolerance. Moreover, they displayed pancreatic islet fibrosis and kidney tubular damage. Despite no signs of overt liver steatosis or dyslipidemia, we found significant changes in the hepatic transcriptome of Nme7+/− male rats with a concerted increase of expression of lipogenic enzymes including Scd1, Fads1, Dhcr7 and a decrease of Cyp7b1 and Nme7. Network analyses suggested possible links between Nme7 and the activation of Srebf1 and Srebf2 upstream regulators. These results further support the implication of NME7 in the pathogenesis of glucose intolerance and adiposity. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Investigations into the Pathogenesis and Pathophysiology of the Metabolic Syndrome)

► Show Figures

Figure 1

Review

Jump to: Research

25 pages, 1632 KiB

Open AccessReview

Genetic Analysis of ABCB4 Mutations and Variants Related to the Pathogenesis and Pathophysiology of Low Phospholipid-Associated Cholelithiasis

by Helen H. Wang, Piero Portincasa, Min Liu and David Q.-H. Wang

Genes 2022, 13(6), 1047; https://doi.org/10.3390/genes13061047 - 11 Jun 2022

Cited by 13 | Viewed by 4486

Abstract

Clinical studies have revealed that the ABCB4 gene encodes the phospholipid transporter on the canalicular membrane of hepatocytes, and its mutations and variants are the genetic basis of low phospholipid-associated cholelithiasis (LPAC), a rare type of gallstone disease caused by a single-gene mutation or variation. The main features of LPAC include a reduction or deficiency of phospholipids in bile, symptomatic cholelithiasis at <40 years of age, intrahepatic sludge and microlithiasis, mild chronic cholestasis, a high cholesterol/phospholipid ratio in bile, and recurrence of biliary symptoms after cholecystectomy. Needle-like cholesterol crystals, putatively “anhydrous” cholesterol crystallization at low phospholipid concentrations in model and native bile, are characterized in ABCB4 knockout mice, a unique animal model for LPAC. Gallbladder bile with only trace amounts of phospholipids in these mice is supersaturated with cholesterol, with lipid composition plotting in the left two-phase zone of the ternary phase diagram, consistent with “anhydrous” cholesterol crystallization. In this review, we summarize the molecular biology and physiological functions of ABCB4 and comprehensively discuss the latest advances in the genetic analysis of ABCB4 mutations and variations and their roles in the pathogenesis and pathophysiology of LPAC in humans, based on the results from clinical studies and mouse experiments. To date, approximately 158 distinct LPAC-causing ABCB4 mutations and variants in humans have been reported in the literature, indicating that it is a monogenic risk factor for LPAC. The elucidation of the ABCB4 function in the liver, the identification of ABCB4 mutations and variants in LPAC patients, and the exploration of gene therapy for ABCB4 deficiency in animal models can help us to better understand the cellular, molecular, and genetic mechanisms underlying the onset of the disease, and will pave the way for early diagnosis and prevention of susceptible subjects and effective intervention for LPAC in patients. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Investigations into the Pathogenesis and Pathophysiology of the Metabolic Syndrome)

► Show Figures

Journal Menu

Journal Browser

Genetic and Epigenetic Investigations into the Pathogenesis and Pathophysiology of the Metabolic Syndrome

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (7 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI