Submit to Cells Review for Cells Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Metabolism".

Deadline for manuscript submissions: closed (30 March 2022) | Viewed by 34340

Share This Special Issue

Special Issue Editor

Prof. Dr. Mohamed Zaiou

E-Mail Website
Guest Editor

School of Pharmacy & The Institute of Jean-Lamour, The University of Lorraine, UMR 7198 CNRS, CEDEX, 54505 Vandoeuvre les Nancy, France
Interests: gene expression; metabolic diseases; biomarkers; epigenetics; precision medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Obesity is a rapidly growing public health concern worldwide. There is therefore an urgent need to develop new preventive and therapeutic strategies for this metabolic disorder.. Tailored diagnosis and therapy of obesity require an understanding of the disease mechanisms and development of novel classifier and predictor biomarkers. In this respect, several research projects are in progress, focusing on epigenome and transcriptional factors (TFs) as frameworks for identifying obesity regulatory mechanisms and hopefully therapeutic strategies.

Researchers now view epigenetic marks and TFs as promising fields that are likely to shed light on the molecular pathogenesis of obesity. Indeed, many investigations have shown that the epigenome, which includes DNA methylation, histone modifications and noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), is involved in the pathogenesis of obesity. Similarly, TFs are known to play a crucial role in this disease and currently, research has renewed interest in these critical gene expression regulators owing to their well-established role in adipogenesis and lipogenesis. Now, if we look at the combined action of epigenetic marks and TFs in the context of obesity, accumulating evidence indicates that both factors may interact to influence gene expression in obesity and associated metabolic diseases. For example, the promoter region of ncRNA genes can contain epigenetic modifications and are implicated in many biological processes through the interaction with TFs. LncRNAs have been reported to alter the transcription of some genes by interacting with TFs, chromatin-modifying complexes, or mRNA. Furthermore, multiple obesity-associated ncRNAs have been identified in adipose tissues and shown to regulate TFs such as PPARγ. Together, these observations suggest an interplay between TFs and epigenome and their implication in the molecular process of obesity.

This Special Issue aims to address the epigenome and TFs regulatory role in obesity and associated metabolic comorbidities. As precision medicine requires precision diagnostics, research in these two fields may result in precision classification, diagnosis, and treatment of patients with obesity and related complications. Thus, original articles, reviews, meta-analyses/systematic review, and case reports that address up-to-date and relevant findings in obesity and related complications (mainly insulin resistance and type 2 diabetes mellitus) are welcome.

Potential topics include but are not limited to the following:

Epigenome, role of DNA methylation, histone modifications and ncRNAs (miRNAs, lncRNAs, circRNAs) in obesity
TFs molecular biology in the regulation of genes associated with obesity
Potential interplay between epigenome and TFs frameworks and their combined impact on obesity and associated complications.

We hope that papers gathered in this Special Issue will bring insights into our understanding of epigenetics and transcriptional mechanisms of genes-causing obesity and obesity-promoted vascular complications and provide us with new ideas for the discovery and the design of new therapeutics.

Prof. Dr. Mohamed Zaiou
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. Cells is an international peer-reviewed open access semimonthly 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 2700 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

Obesity and related metabolic diseases
Epigenetic marks
Transcription factors
Noncoding RNAs (ncRNAs)
Interplay between transcription factors and epigenome
Metabolic diseases
Gene expression

Published Papers (11 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research, Review

3 pages, 200 KiB

Open AccessEditorial

Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities

by Mohamed Zaiou

Cells 2022, 11(16), 2520; https://doi.org/10.3390/cells11162520 - 14 Aug 2022

Cited by 1 | Viewed by 1051

Abstract

Recent advances in the study of chromatin remodeling and transcriptional machinery complex dysfunction, and how they drive metabolic-related gene expression have considerably increased our understanding of several molecular processes underlaying obesity and its complications [...] Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

Research

Jump to: Editorial, Review

17 pages, 1450 KiB

Open AccessArticle

Cumulative Metabolic and Epigenetic Effects of Paternal and/or Maternal Supplementation with Arachidonic Acid across Three Consecutive Generations in Mice

by Carmen de la Rocha, Dalia Rodríguez-Ríos, Enrique Ramírez-Chávez, Jorge Molina-Torres, José de Jesús Flores-Sierra, Luis M. Orozco-Castellanos, Juan P. Galván-Chía, Atenea Vázquez Sánchez, Silvio Zaina and Gertrud Lund

Cells 2022, 11(6), 1057; https://doi.org/10.3390/cells11061057 - 21 Mar 2022

Cited by 7 | Viewed by 2651

Abstract

Apart from the known associations between arachidonic acid (AA), weight gain, and neurological and immune function, AA exposure leads to alterations in global and gene-specific DNA methylation (DNAm) and fatty acid (FA) content in human cultured cells. However, it is unknown as to whether the latter effects occur in vivo and are maintained over extended periods of time and across generations. To address this issue, we asked whether AA supplementation for three consecutive generations (prior to coitus in sires or in utero in dams) affected offspring growth phenotypes, in addition to liver DNAm and FA profiles in mice. Twelve-week-old BALB/c mice were exposed daily to AA dissolved in soybean oil (vehicle, VH), or VH only, for 10 days prior to mating or during the entire pregnancy (20 days). On average, 15 mice were supplemented per generation, followed by analysis of offspring body weight and liver traits (x average = 36 and 10 per generation, respectively). Body weight cumulatively increased in F2 and F3 offspring generations and positively correlated with milligrams of paternal or maternal offspring AA exposure. A concomitant increase in liver weight was observed. Notably, akin to AA-challenged cultured cells, global DNAm and cis-7-hexadecenoic acid (16:1n-9), an anti-inflammatory FA that is dependent on stearoyl-CoA desaturase 1 (SCD1) activity, increased with milligrams of AA exposure. In accordance, liver Scd1 promoter methylation decreased with milligrams of germline AA exposure and was negatively correlated with liver weight. Our results show that mice retain cellular memories of AA exposure across generations that could potentially be beneficial to the innate immune system. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Figure 1

19 pages, 4724 KiB

Open AccessArticle

Salvia miltiorrhiza Extract and Individual Synthesized Component Derivatives Induce Activating-Transcription-Factor-3-Mediated Anti-Obesity Effects and Attenuate Obesity-Induced Metabolic Disorder by Suppressing C/EBPα in High-Fat-Induced Obese Mice

by Yueh-Lin Wu, Heng Lin, Hsiao-Fen Li, Ming-Jaw Don, Pei-Chih King and Hsi-Hsien Chen

Cells 2022, 11(6), 1022; https://doi.org/10.3390/cells11061022 - 17 Mar 2022

Cited by 6 | Viewed by 3238

Abstract

Pharmacological studies indicate that Salvia miltiorrhiza extract (SME) can improve cardiac and blood vessel function. However, there is limited knowledge regarding the effects (exerted through epigenetic regulation) of SME and newly derived single compounds, with the exception of tanshinone IIA and IB, on obesity-induced metabolic disorders. In this study, we administered SME or dimethyl sulfoxide (DMSO) as controls to male C57BL/J6 mice after they were fed a high-fat diet (HFD) for 4 weeks. SME treatment significantly reduced body weight, fasting plasma glucose, triglyceride levels, insulin resistance, and adipogenesis/lipogenesis gene expression in treated mice compared with controls. Transcriptome array analysis revealed that the expression of numerous transcriptional factors, including activating transcription factor 3 (ATF3) and C/EBPα homologous protein (CHOP), was significantly higher in the SME group. ST32db, a novel synthetic derivative similar in structure to compounds from S. miltiorrhiza extract, ameliorates obesity and obesity-induced metabolic syndrome in HFD-fed wild-type mice but not ATF3^−/− mice. ST32db treatment of 3T3-L1 adipocytes suppresses lipogenesis/adipogenesis through the ATF3 pathway to directly inhibit C/EBPα expression and indirectly inhibit the CHOP pathway. Overall, ST32db, a single compound modified from S. miltiorrhiza extract, has anti-obesity effects through ATF3-mediated C/EBPα downregulation and the CHOP pathway. Thus, SME and ST32db may reduce obesity and diabetes in mice, indicating the potential of both SME and ST32db as therapeutic drugs for the treatment of obesity-induced metabolic syndrome. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Graphical abstract

16 pages, 1563 KiB

Open AccessEditor’s ChoiceArticle

Epigenetic Dysregulation of the Homeobox A5 (HOXA5) Gene Associates with Subcutaneous Adipocyte Hypertrophy in Human Obesity

by Luca Parrillo, Rosa Spinelli, Mattia Costanzo, Pasqualina Florese, Serena Cabaro, Antonella Desiderio, Immacolata Prevenzano, Gregory Alexander Raciti, Ulf Smith, Claudia Miele, Pietro Formisano, Raffaele Napoli and Francesco Beguinot

Cells 2022, 11(4), 728; https://doi.org/10.3390/cells11040728 - 18 Feb 2022

Cited by 6 | Viewed by 2167

Abstract

Along with insulin resistance and increased risk of type 2 diabetes (T2D), lean first-degree relatives of T2D subjects (FDR) feature impaired adipogenesis in subcutaneous adipose tissue (SAT) and subcutaneous adipocyte hypertrophy well before diabetes onset. The molecular mechanisms linking these events have only partially been clarified. In the present report, we show that silencing of the transcription factor Homeobox A5 (HOXA5) in human preadipocytes impaired differentiation in mature adipose cells in vitro. The reduced adipogenesis was accompanied by inappropriate WNT-signaling activation. Importantly, in preadipocytes from FDR individuals, HOXA5 expression was attenuated, with hypermethylation of the HOXA5 promoter region found responsible for its downregulation, as revealed by luciferase assay. Both HOXA5 gene expression and DNA methylation were significantly correlated with SAT adipose cell hypertrophy in FDR, whose increased adipocyte size marks impaired adipogenesis. In preadipocytes from FDR, the low HOXA5 expression negatively correlated with enhanced transcription of the WNT signaling downstream genes NFATC1 and WNT2B. In silico evidence indicated that NFATC1 and WNT2B were directly controlled by HOXA5. The HOXA5 promoter region also was hypermethylated in peripheral blood leukocytes from these same FDR individuals, which was further revealed in peripheral blood leukocytes from an independent group of obese subjects. Thus, HOXA5 controlled adipogenesis in humans by suppressing WNT signaling. Altered DNA methylation of the HOXA5 promoter contributed to restricted adipogenesis in the SAT of lean subjects who were FDR of type 2 diabetics and in obese individuals. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Figure 1

18 pages, 9196 KiB

Open AccessArticle

MXD3 Promotes Obesity and the Androgen Receptor Signaling Pathway in Gender-Disparity Hepatocarcinogenesis

by Yi-Wen Tsai, Kuo-Shyang Jeng, Mu-Kuang He, Yang-Wen Hsieh, Hsin-Hung Lai, Chi-Yu Lai, Chun-Chieh Huang, Chiung-Fang Chang, Chung-Tsui Huang and Guor Mour Her

Cells 2021, 10(12), 3434; https://doi.org/10.3390/cells10123434 - 06 Dec 2021

Cited by 2 | Viewed by 3370

Abstract

Obesity is closely linked to metabolic diseases, particularly non-alcoholic steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD), ultimately leading to hepatocellular carcinoma (HCC). However, the molecular mechanisms of NASH-associated HCC (NAHCC) remain elusive. To explore the impact of Max dimerization protein 3 (MXD3), a transcription factor that regulates several cellular functions in disorders associated with metabolic diseases, we conditionally expressed Mxd3 proteins using Tet-on mxd3 transgenic zebrafish (MXs) with doxycycline (MXs + Dox) or without doxycycline (MXs − Dox) treatment. Overexpression of global MXD3 (gMX) or hepatic Mxd3 (hMX) was associated with obesity-related NAFLD pathophysiology in gMX + Dox, and liver fibrosis and HCC in hMX + Dox. Oil Red O (ORO)-stained signals were seen in intravascular blood vessels and liver buds of larval gMX + Dox, indicating that Mxd3 functionally promotes lipogenesis. The gMX + Dox-treated young adults exhibited an increase in body weight and visceral fat accumulation. The hMX + Dox-treated young adults showed normal body characteristics but exhibited liver steatosis and NASH-like phenotypes. Subsequently, steatohepatitis, liver fibrosis, and NAHCC were found in 6-month-old gMX + Dox adults compared with gMX − Dox adults at the same stage. Overexpression of Mxd3 also enhanced AR expression accompanied by the increase of AR-signaling pathways resulting in hepatocarcinogenesis in males. Our results demonstrate that global actions of Mxd3 are central to the initiation of obesity in the gMX zebrafish through their effects on adipogenesis and that MXD3 could serve as a therapeutic target for obesity-associated liver diseases. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Graphical abstract

19 pages, 4242 KiB

Open AccessArticle

High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway

by Yan Huang, Hui-Min Liu, Qian-Ying Mao, Xin Cong, Yan Zhang, Sang-Woo Lee, Kyungpyo Park, Li-Ling Wu, Ruo-Lan Xiang and Guang-Yan Yu

Cells 2021, 10(11), 3230; https://doi.org/10.3390/cells10113230 - 19 Nov 2021

Cited by 9 | Viewed by 2240

Abstract

Tight junctions (TJs) play an important role in water, ion, and solute transport through the paracellular pathway of epithelial cells; however, their role in diabetes-induced salivary gland dysfunction remains unknown. Here, we found that the TJ proteins claudin-1 and claudin-3 were significantly increased in the submandibular glands (SMGs) of db/db mice and high glucose (HG)-treated human SMGs. HG decreased paracellular permeability and increased claudin-1 and claudin-3 expression in SMG-C6 cells. Knockdown of claudin-1 or claudin-3 reversed the HG-induced decrease in paracellular permeability. MiR-22-3p was significantly downregulated in diabetic SMGs and HG-treated SMG-C6 cells. A miR-22-3p mimic suppressed claudin-1 and claudin-3 expression and abolished the HG-induced increases in claudin-1 and claudin-3 levels in SMG-C6 cells, whereas a miR-22-3p inhibitor produced the opposite effects. Specificity protein-1 (Sp1) was enhanced in diabetic SMGs and HG-treated SMG-C6 cells, which promoted claudin-1 and claudin-3 transcription through binding to the corresponding promoters. A luciferase reporter assay confirmed that miR-22-3p repressed Sp1 by directly targeting the Sp1 mRNA 3′-untranslated region (3′-UTR). Consistently, the miR-22-3p mimic suppressed, whereas the miR-22-3p inhibitor enhanced, the effects of HG on Sp1 expression. Taken together, our results demonstrate a new regulatory pathway through which HG decreases the paracellular permeability of SMG cells by inhibiting miR-22-3p/Sp1-mediated claudin-1 and claudin-3 expression. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Figure 1

16 pages, 3930 KiB

Open AccessArticle

Epigenetic Regulation of Peroxisome Proliferator-Activated Receptor Gamma Mediates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease

by Tahar Hajri, Mohamed Zaiou, Thomas V. Fungwe, Khadija Ouguerram and Samuel Besong

Cells 2021, 10(6), 1355; https://doi.org/10.3390/cells10061355 - 31 May 2021

Cited by 25 | Viewed by 4025

Abstract

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in Western countries and has become a serious public health concern. Although Western-style dietary patterns, characterized by a high intake of saturated fat, is considered a risk factor for NAFLD, the molecular mechanisms leading to hepatic fat accumulation are still unclear. In this study, we assessed epigenetic regulation of peroxisome proliferator-activated receptor γ (PPARγ), modifications of gene expression, and lipid uptake in the liver of mice fed a high-fat diet (HFD), and in hepatocyte culture challenged with palmitic acid. Bisulfate pyrosequencing revealed that HFD reduced the level of cytosine methylation in the pparγ DNA promoter. This was associated with increased expression of the hepatic PPARγ, very low-density lipoprotein receptor (VLDLR) and cluster differentiating 36 (CD36), and enhanced uptake of fatty acids and very low-density lipoprotein, leading to excess hepatic lipid accumulation. Furthermore, palmitic acid overload engendered comparable modifications in hepatocytes, suggesting that dietary fatty acids contribute to the pathogenesis of NAFLD through epigenetic upregulation of PPARγ and its target genes. The significance of epigenetic regulation was further demonstrated in hepatocytes treated with DNA methylation inhibitor, showing marked upregulation of PPARγ and its target genes, leading to enhanced fatty acid uptake and storage. This study demonstrated that HFD-induction of pparγ DNA promoter demethylation increased the expression of PPARγ and its target genes, vldlr and cd36, leading to excess lipid accumulation, an important initiating mechanism by which HFD increased PPARγ and lipid accumulation. These findings provide strong evidence that modification of the pparγ promoter methylation is a crucial mechanism of regulation in NAFLD pathogenesis. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Figure 1

15 pages, 1482 KiB

Open AccessArticle

The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes

by Cécilia Colson, Pierre-Louis Batrow, Nadine Gautier, Nathalie Rochet, Gérard Ailhaud, Franck Peiretti and Ez-Zoubir Amri

Cells 2020, 9(11), 2433; https://doi.org/10.3390/cells9112433 - 07 Nov 2020

Cited by 8 | Viewed by 2420

Abstract

Thermogenic brown and brite adipocytes convert chemical energy from nutrients into heat. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to control fat mass such as in obesity or cachexia. The peroxisome proliferator-activated receptor (PPAR) family plays key roles in the maintenance of adipose tissue and in the regulation of thermogenic activity. Activation of these receptors induce browning of white adipocyte. The purpose of this work was to characterize the role of carnosic acid (CA), a compound used in traditional medicine, in the control of brown/brite adipocyte formation and function. We used human multipotent adipose-derived stem (hMADS) cells differentiated into white or brite adipocytes. The expression of key marker genes was determined using RT-qPCR and western blotting. We show here that CA inhibits the browning of white adipocytes and favors decreased gene expression of thermogenic markers. CA treatment does not affect β-adrenergic response. Importantly, the effects of CA are fully reversible. We used transactivation assays to show that CA has a PPARα/γ antagonistic action. Our data pinpoint CA as a drug able to control PPAR activity through an antagonistic effect. These observations shed some light on the development of natural PPAR antagonists and their potential effects on thermogenic response. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Figure 1

22 pages, 5282 KiB

Open AccessArticle

Repetitive Intermittent Hyperglycemia Drives the M1 Polarization and Inflammatory Responses in THP-1 Macrophages Through the Mechanism Involving the TLR4-IRF5 Pathway

by Fatema Al-Rashed, Sardar Sindhu, Hossein Arefanian, Ashraf Al Madhoun, Shihab Kochumon, Reeby Thomas, Sarah Al-Kandari, Abdulwahab Alghaith, Texy Jacob, Fahd Al-Mulla and Rasheed Ahmad

Cells 2020, 9(8), 1892; https://doi.org/10.3390/cells9081892 - 12 Aug 2020

Cited by 32 | Viewed by 4685

Abstract

Repetitive intermittent hyperglycemia (RIH) is an independent risk factor for complications associated with type-2 diabetes (T2D). Glucose fluctuations commonly occur in T2D patients with poor glycemic control or following intensive therapy. Reducing blood glucose as well as glucose fluctuations is critical to the control of T2D and its macro-/microvascular complications. The interferon regulatory factor (IRF)-5 located downstream of the nutrient sensor toll-like receptor (TLR)-4, is emerging as a key metabolic regulator. It remains unclear how glucose fluctuations may alter the IRF5/TLR4 expression and inflammatory responses in monocytes/macrophages. To investigate this, first, we determined IRF5 gene expression by real-time qRT-PCR in the white adipose tissue samples from 39 T2D and 48 nondiabetic individuals. Next, we cultured THP-1 macrophages in hypo- and hyperglycemic conditions and compared, at the protein and transcription levels, the expressions of IRF5, TLR4, and M1/M2 polarization profile and inflammatory markers against control (normoglycemia). Protein expression was assessed using flow cytometry, ELISA, Western blotting, and/or confocal microscopy. IRF5 silencing was achieved by small interfering RNA (siRNA) transfection. The data show that adipose IRF5 gene expression was higher in T2D than nondiabetic counterparts (p = 0.006), which correlated with glycated hemoglobin (HbA1c) (r = 0.47/p < 0.001), homeostatic model assessment of insulin resistance (HOMA-IR) (r = 0.23/p = 0.03), tumor necrosis factor (TNF)-α (r = 0.56/p < 0.0001), interleukin (IL)-1β (r = 0.40/p = 0.0009), and C-C motif chemokine receptor (CCR)-2 (r = 0.49/p < 0.001) expression. IRF5 expression in macrophages was induced/upregulated (p < 0.05) by hypoglycemia (3 mM/L), persistent hyperglycemia (15 mM/L–25 mM/L), and RIH/glucose fluctuations (3–15 mM/L) as compared to normoglycemia (5 mM/L). RIH/glucose fluctuations also induced M1 polarization and an inflammatory profile (CD11c, IL-1β, TNF-α, IL-6, and monocyte chemoattractant protein (MCP)-1) in macrophages. RIH/glucose fluctuations also drove the expression of matrix metalloproteinase (MMP)-9 (p < 0.001), which is a known marker for cardiovascular complication in T2D patients. Notably, all these changes were counteracted by IRF5 silencing in macrophages. In conclusion, RIH/glucose fluctuations promote the M1 polarization and inflammatory responses in macrophages via the mechanism involving TLR4-IRF5 pathway, which may have significance for metabolic inflammation. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

14 pages, 1890 KiB

Open AccessReview

How (Epi)Genetic Regulation of the LIM-Domain Protein FHL2 Impacts Multifactorial Disease

by Jayron J. Habibe, Maria P. Clemente-Olivo and Carlie J. de Vries

Cells 2021, 10(10), 2611; https://doi.org/10.3390/cells10102611 - 01 Oct 2021

Cited by 6 | Viewed by 3153

Abstract

Susceptibility to complex pathological conditions such as obesity, type 2 diabetes and cardiovascular disease is highly variable among individuals and arises from specific changes in gene expression in combination with external factors. The regulation of gene expression is determined by genetic variation (SNPs) and epigenetic marks that are influenced by environmental factors. Aging is a major risk factor for many multifactorial diseases and is increasingly associated with changes in DNA methylation, leading to differences in gene expression. Four and a half LIM domains 2 (FHL2) is a key regulator of intracellular signal transduction pathways and the FHL2 gene is consistently found as one of the top hyper-methylated genes upon aging. Remarkably, FHL2 expression increases with methylation. This was demonstrated in relevant metabolic tissues: white adipose tissue, pancreatic β-cells, and skeletal muscle. In this review, we provide an overview of the current knowledge on regulation of FHL2 by genetic variation and epigenetic DNA modification, and the potential consequences for age-related complex multifactorial diseases. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Graphical abstract

18 pages, 706 KiB

Open AccessReview

The Emerging Role and Promise of Circular RNAs in Obesity and Related Metabolic Disorders

by Mohamed Zaiou

Cells 2020, 9(6), 1473; https://doi.org/10.3390/cells9061473 - 16 Jun 2020

Cited by 28 | Viewed by 3468

Abstract

Circular RNAs (circRNAs) are genome transcripts that are produced from back-splicing of specific regions of pre-mRNA. These single-stranded RNA molecules are widely expressed across diverse phyla and many of them are stable and evolutionary conserved between species. Growing evidence suggests that many circRNAs function as master regulators of gene expression by influencing both transcription and translation processes. Mechanistically, circRNAs are predicted to act as endogenous microRNA (miRNA) sponges, interact with functional RNA-binding proteins (RBPs), and associate with elements of the transcriptional machinery in the nucleus. Evidence is mounting that dysregulation of circRNAs is closely related to the occurrence of a range of diseases including cancer and metabolic diseases. Indeed, there are several reports implicating circRNAs in cardiovascular diseases (CVD), diabetes, hypertension, and atherosclerosis. However, there is very little research addressing the potential role of these RNA transcripts in the occurrence and development of obesity. Emerging data from in vitro and in vivo studies suggest that circRNAs are novel players in adipogenesis, white adipose browning, obesity, obesity-induced inflammation, and insulin resistance. This study explores the current state of knowledge on circRNAs regulating molecular processes associated with adipogenesis and obesity, highlights some of the challenges encountered while studying circRNAs and suggests some perspectives for future research directions in this exciting field of study. Full article

(This article belongs to the Special Issue Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities)

► Show Figures

Journal Menu

Journal Browser

Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI