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Molecular Research on Metabolic Disorders
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Molecular Research on Metabolic Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 58164

Special Issue Editors

Prof. Dr. Maria S. Fernandez-Alfonso

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Guest Editor
Instituto Pluridisciplinar and Facultad de Farmacia, Universidad Complutense, Madrid, Spain
Special Issues, Collections and Topics in MDPI journals
Dr. Marta Gil-Ortega

E-Mail Website
Guest Editor
Department of Pharmaceutical and Health Sciences, San Pablo CEU University, Ctra. Boadilla del Monte Km5.300, 28925-Alcorcón, Spain
Interests: obesity; blood pressure
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic disorders are nowadays considered as a major health problem affecting a huge percentage of the population worldwide. They are associated with chronic diseases like obesity, diabetes, non-alcoholic fatty liver disease, or cardiovascular alterations among others, as well as with a higher incidence of all-cause mortality.

For the last few years, a large number of studies have deepened and progressed our knowledge of the molecular mechanisms involved in the development of metabolic disorders. In this regard, special attention has been focused on oxidative stress, inflammation, endoplasmic reticulum stress, alterations on glucose and/or lipid metabolism, insulin resistance, endothelial dysfunction, etc. Nevertheless, further studies are required in order to identify new potential mechanisms implicated in the development of these alterations and/or potential targets (i.e., new adipokines, signaling molecules, exosomes, epigenetic reprogramming, biomarkers, etc.) that could help to develop new strategies and drugs aimed at preventing and/or reversing the complications associated with metabolic disorders.

This Special Issue aims to review current advances in the field of metabolic disorders associated with obesity, diabetes, and non-alcoholic fatty liver and cardiovascular disease with the purpose of better understanding the pathways involved in these alterations. Contributions to both animal models and/or humans are encouraged to shed light on the development of new therapeutic approaches to improve the clinical management of cardiometabolic complications derived from metabolic disorders.

Prof. Dr. Maria S Fernandez-Alfonso
Prof. Dr. Marta Gil-Ortega
Guest Editors

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Keywords

  • obesity
  • diabetes
  • insulin resistance
  • oxidative stress
  • inflammation
  • non-alcoholic fatty liver disease
  • cardiovascular alterations
  • endoplasmic reticulum stress
  • lipids
  • glucose
  • adipokines
  • exosomes
  • epigenetics
  • biomarkers

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Published Papers (11 papers)

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15 pages, 3557 KiB  
Article
The Cooperative Induction of CCL4 in Human Monocytic Cells by TNF-α and Palmitate Requires MyD88 and Involves MAPK/NF-κB Signaling Pathways
by Sardar Sindhu, Shihab Kochumon, Steve Shenouda, Ajit Wilson, Fahd Al-Mulla and Rasheed Ahmad
Int. J. Mol. Sci. 2019, 20(18), 4658; https://doi.org/10.3390/ijms20184658 - 19 Sep 2019
Cited by 44 | Viewed by 7901
Abstract
Chronic low-grade inflammation, also known as metabolic inflammation, is a hallmark of obesity and parallels with the presence of elevated circulatory levels of free fatty acids and inflammatory cytokines/chemokines. CCL4/MIP-1β chemokine plays a key role in the adipose tissue monocyte recruitment. Increased circulatory [...] Read more.
Chronic low-grade inflammation, also known as metabolic inflammation, is a hallmark of obesity and parallels with the presence of elevated circulatory levels of free fatty acids and inflammatory cytokines/chemokines. CCL4/MIP-1β chemokine plays a key role in the adipose tissue monocyte recruitment. Increased circulatory levels of TNF-α, palmitate and CCL4 are co-expressed in obesity. We asked if the TNF-α/palmitate could interact cooperatively to augment the CCL4 production in human monocytic cells and macrophages. THP-1 cells/primary macrophages were co-treated with TNF-α/palmitate and CCL4 mRNA/protein expression was assessed using qRT-PCR/ELISA. TLR4 siRNA, a TLR4 receptor-blocking antibody, XBlue™-defMyD cells and pathway inhibitors were used to decipher the signaling mechanisms. We found that TNF-α/palmitate co-stimulation augmented the CCL4 expression in monocytic cells and macrophages compared to controls (p < 0.05). TLR4 suppression or neutralization abrogated the CCL4 expression in monocytic cells. Notably, CCL4 cooperative induction in monocytic cells was: (1) Markedly less in MyD88-deficient cells, (2) IRF3 independent, (3) clathrin dependent and (4) associated with the signaling mechanism involving ERK1/2, c-Jun, JNK and NF-κB. In conclusion, TNF-α/palmitate co-stimulation promotes the CCL4 expression in human monocytic cells through the mechanism involving a TLR4-MyD88 axis and MAPK/NF-κB pathways. These findings unravel a novel mechanism of the cooperative induction of CCL4 by TNF-α and palmitate which could be relevant to metabolic inflammation. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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11 pages, 970 KiB  
Article
Bone Matrix Levels of Dickkopf and Sclerostin are Positively Correlated with Bone Mass and Strength in Postmenopausal Osteoporosis
by Thor Ueland, Lis Stilgren and Jens Bollerslev
Int. J. Mol. Sci. 2019, 20(12), 2896; https://doi.org/10.3390/ijms20122896 - 14 Jun 2019
Cited by 28 | Viewed by 3931
Abstract
Wnt signaling plays a pivotal role in maintaining bone mass. Secreted pathway modulators such as sclerostin (SOST) and Dickkopfs (DKKs) may influence bone mass inhibiting the canonical Wnt pathway. We evaluated whether bone protein content of secreted Wnt antagonists is related to age, [...] Read more.
Wnt signaling plays a pivotal role in maintaining bone mass. Secreted pathway modulators such as sclerostin (SOST) and Dickkopfs (DKKs) may influence bone mass inhibiting the canonical Wnt pathway. We evaluated whether bone protein content of secreted Wnt antagonists is related to age, bone mass, and strength in postmenopausal osteoporosis. We measured cortical and trabecular bone contents of SOST and Dickkopf-1 (DKK1) in combined extracts obtained after ethylenediaminetetraacetic acid and guanidine hydrochloride extraction in 56 postmenopausal women aged 47–74 (mean, 63) yr with a previous distal forearm fracture and a hip or spine Z-score less than 0. Our findings were (i) SOST and DKK1 protein levels were higher in trabecular bone, (ii) cortical and trabecular DKK1 and trabecular SOST correlated positively with bone matrix levels of osteocalcin (r between 0.28 and 0.45, p < 0.05), (iii) cortical DKK1 correlated with lumbar spine bone mineral density (BMD) (r = 0.32, p < 0.05) and femoral neck BMD (r = 0.41, p < 0.01), and (iv) cortical DKK1 and SOST correlated with apparent bone volumetric density and compressive strength (r between 0.34 and 0.51, p < 0.01). In conclusion, cortical bone matrix levels of DKK1 and SOST were positively correlated with bone mass and bone strength in postmenopausal osteoporotic women. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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12 pages, 575 KiB  
Article
Effect of Peritoneal Dialysis on Serum Fibrosis Biomarkers in Patients with Refractory Congestive Heart Failure
by Margarita Kunin, Vered Carmon, Pazit Beckerman and Dganit Dinour
Int. J. Mol. Sci. 2019, 20(11), 2610; https://doi.org/10.3390/ijms20112610 - 28 May 2019
Cited by 3 | Viewed by 2680
Abstract
Background: Cardiac collagen remodeling is important in the progression of heart failure. Estimation of cardiac collagen turnover by serum levels of serological markers is used for monitoring cardiac tissue repair and fibrosis. Peritoneal dialysis (PD) is used for the long-term management of refractory [...] Read more.
Background: Cardiac collagen remodeling is important in the progression of heart failure. Estimation of cardiac collagen turnover by serum levels of serological markers is used for monitoring cardiac tissue repair and fibrosis. Peritoneal dialysis (PD) is used for the long-term management of refractory congestive heart failure (CHF). In this study, we investigated the effect of PD treatment on circulating fibrosis markers levels in patients with refractory CHF and fluid overload. Methods: Twenty-five patients with refractory CHF treated with PD were prospectively enrolled in the study. Circulating fibrosis markers procollagen type III C-peptide (PIIINP), matrix metalloproteinase 2 (MMP-2), and tissue inhibitor of metalloproteinases I (TIMP-1) levels were checked at baseline and after three and six months of treatment. Results: The clinical benefit of PD manifested by improved NYHA functional class and reduced hospitalization rate. Serum brain natriuretic peptide (BNP) levels decreased significantly during the treatment. Serum MMP-2 and TIMP-1 decreased significantly on PD. Circulating PIIINP showed two patterns of change, either decreased or increased following PD treatment. Patients in whom circulating PIIINP decreased had significantly lower baseline serum albumin, lower baseline mean arterial blood pressure, higher serum CRP, and a less significant improvement in hospitalization rate compared to the patients in whom circulating PIIINP increased. Patients in whom all three markers decreased demonstrated a trend to longer survival compared to patients whose markers increased or did not change. Conclusion: In refractory CHF patients PD treatment was associated with a reduction in circulating fibrosis markers. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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25 pages, 3895 KiB  
Article
Multiple Glycation Sites in Blood Plasma Proteins as an Integrated Biomarker of Type 2 Diabetes Mellitus
by Alena Soboleva, Gregory Mavropulo-Stolyarenko, Tatiana Karonova, Domenika Thieme, Wolfgang Hoehenwarter, Christian Ihling, Vasily Stefanov, Tatiana Grishina and Andrej Frolov
Int. J. Mol. Sci. 2019, 20(9), 2329; https://doi.org/10.3390/ijms20092329 - 10 May 2019
Cited by 27 | Viewed by 4374
Abstract
Type 2 diabetes mellitus (T2DM) is one of the most widely spread metabolic diseases. Because of its asymptomatic onset and slow development, early diagnosis and adequate glycaemic control are the prerequisites for successful T2DM therapy. In this context, individual amino acid residues might [...] Read more.
Type 2 diabetes mellitus (T2DM) is one of the most widely spread metabolic diseases. Because of its asymptomatic onset and slow development, early diagnosis and adequate glycaemic control are the prerequisites for successful T2DM therapy. In this context, individual amino acid residues might be sensitive indicators of alterations in blood glycation levels. Moreover, due to a large variation in the half-life times of plasma proteins, a generalized biomarker, based on multiple glycation sites, might provide comprehensive control of the glycemic status across any desired time span. Therefore, here, we address the patterns of glycation sites in highly-abundant blood plasma proteins of T2DM patients and corresponding age- and gender-matched controls by comprehensive liquid chromatography-mass spectrometry (LC-MS). The analysis revealed 42 lysyl residues, significantly upregulated under hyperglycemic conditions. Thereby, for 32 glycation sites, biomarker behavior was demonstrated here for the first time. The differentially glycated lysines represented nine plasma proteins with half-lives from 2 to 21 days, giving access to an integrated biomarker based on multiple protein-specific Amadori peptides. The validation of this biomarker relied on linear discriminant analysis (LDA) with random sub-sampling of the training set and leave-one-out cross-validation (LOOCV), which resulted in an accuracy, specificity, and sensitivity of 92%, 100%, and 85%, respectively. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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12 pages, 4073 KiB  
Article
Changes of Circulating Extracellular Vesicles from the Liver after Roux-en-Y Bariatric Surgery
by Gersina Rega-Kaun, Dorothea Ritzel, Christoph Kaun, Benjamin Ebenbauer, Barbara Thaler, Manfred Prager, Svitlana Demyanets, Johann Wojta and Philipp J. Hohensinner
Int. J. Mol. Sci. 2019, 20(9), 2153; https://doi.org/10.3390/ijms20092153 - 30 Apr 2019
Cited by 11 | Viewed by 3108
Abstract
Circulating extracellular vesicles are small particles enclosed by a phospholipid bilayer. Vesicles deriving directly from the cellular membrane by an active budding process retain cell origin specific proteins and RNA. These vesicles carry pathophysiological information from their parental cell and hold the potential [...] Read more.
Circulating extracellular vesicles are small particles enclosed by a phospholipid bilayer. Vesicles deriving directly from the cellular membrane by an active budding process retain cell origin specific proteins and RNA. These vesicles carry pathophysiological information from their parental cell and hold the potential to allow analysis of organs without the need for a biopsy. We included in our study 27 patients undergoing bariatric surgery. Hepatic extracellular vesicles were determined by flow cytometry. mRNA specific for hepatic cellular origin was determined in the extracellular vesicle fraction using qPCR. Surgery led to a massive reduction of weight and overall hepatic stress as determined by alanine transaminase (ALT), aspartate transaminase (AST) and γ-glutamyltransferase (GGT). Total extracellular vesicle numbers were reduced after bariatric surgery. Liver specific vesicles identified by HepPar1 or asialoglycoprotein receptor (ASGPR) were significantly reduced after bariatric surgery in both AnnexinV+ and AnnexinV− subgroups. When analyzing circulating liver-specific mRNAs, we found reduced levels of these mRNAs after surgery even though total circulating RNA remained unchanged. We conclude that circulating hepatic extracellular vesicles are detectable in samples from patients undergoing gastric bypass surgery. These vesicles are reduced after a reduction of hepatic stress also observed with classic liver enzyme measurements. We conclude that ASGPR or HepPar positive vesicles hold the potential to serve as liver specific vesicle markers. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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15 pages, 2004 KiB  
Article
Cell Signaling Pathways in Mammary Carcinoma Induced in Rats with Low versus High Inherent Aerobic Capacity
by Tymofiy Lutsiv, John N. McGinley, Elizabeth S. Neil and Henry J. Thompson
Int. J. Mol. Sci. 2019, 20(6), 1506; https://doi.org/10.3390/ijms20061506 - 26 Mar 2019
Cited by 2 | Viewed by 3563
Abstract
An inverse association exists between physical activity and breast cancer incidence and outcomes. An objective indicator of an individual’s recent physical activity exposure is aerobic capacity. We took advantage of the fact that there is an inherited as well as inducible component of [...] Read more.
An inverse association exists between physical activity and breast cancer incidence and outcomes. An objective indicator of an individual’s recent physical activity exposure is aerobic capacity. We took advantage of the fact that there is an inherited as well as inducible component of aerobic capacity to show that experimentally induced mammary cancer is inversely related to inherent aerobic capacity (IAC). The objective of this study was to determine whether cell signaling pathways involved in the development of mammary cancer differed in rats with low inherent aerobic capacity (LIAC, n = 55) versus high inherent aerobic capacity (HIAC, n = 57). Cancer burden was 0.21 ± 0.16 g/rat in HIAC versus 1.14 ± 0.45 in LIAC, p < 0.001. Based on protein expression, cancer in LIAC animals was associated with upregulated glucose utilization, and protein and fatty acid synthesis. Signaling in cancers from HIAC rats was associated with energy sensing, fatty acid oxidation and cell cycle arrest. These findings support the thesis that pro-glycolytic, metabolic inflexibility in LIAC favors not only insulin resistance and obesity but also tumor development and growth. This provides an unappreciated framework for understanding how obesity and low aerobic fitness, hallmarks of physical inactivity, are associated with higher cancer risk and poorer prognosis. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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19 pages, 2437 KiB  
Article
Endothelial Progenitor Cells as Pathogenetic and Diagnostic Factors, and Potential Targets for GLP-1 in Combination with Metabolic Syndrome and Chronic Obstructive Pulmonary Disease
by Evgenii Germanovich Skurikhin, Olga Victorovna Pershina, Angelina Vladimirovna Pakhomova, Edgar Sergeevich Pan, Vyacheslav Andreevich Krupin, Natalia Nicolaevna Ermakova, Olga Evgenevna Vaizova, Anna Sergeevna Pozdeeva, Mariia Andreevna Zhukova, Viktoriia Evgenevna Skurikhina, Wolf-Dieter Grimm and Alexander Mikhaylovich Dygai
Int. J. Mol. Sci. 2019, 20(5), 1105; https://doi.org/10.3390/ijms20051105 - 4 Mar 2019
Cited by 16 | Viewed by 4870
Abstract
In clinical practice, there are patients with a combination of metabolic syndrome (MS) and chronic obstructive pulmonary disease (COPD). The pathological mechanisms linking MS and COPD are largely unknown. It remains unclear whether the effect of MS (possible obesity) has a major impact [...] Read more.
In clinical practice, there are patients with a combination of metabolic syndrome (MS) and chronic obstructive pulmonary disease (COPD). The pathological mechanisms linking MS and COPD are largely unknown. It remains unclear whether the effect of MS (possible obesity) has a major impact on the progression of COPD. This complicates the development of effective approaches for the treatment of patients with a diagnosis of MS and COPD. Experiments were performed on female C57BL/6 mice. Introduction of monosodium glutamate and extract of cigarette smoke was modeled to simulate the combined pathology of lipid disorders and emphysema. Biological effects of glucagon-like peptide 1 (GLP-1) and GLP-1 on endothelial progenitor cells (EPC) in vitro and in vivo were evaluated. Histological, immunohistochemical methods, biochemical methods, cytometric analysis of markers identifying EPC were used in the study. The CD31+ endothelial cells in vitro evaluation was produced by Flow Cytometry and Image Processing of each well with a Cytation™ 3. GLP-1 reduces the area of emphysema and increases the number of CD31+ endothelial cells in the lungs of mice in conditions of dyslipidemia and damage to alveolar tissue of cigarette smoke extract. The regenerative effects of GLP-1 are caused by a decrease in inflammation, a positive effect on lipid metabolism and glucose metabolism. EPC are proposed as pathogenetic and diagnostic markers of endothelial disorders in combination of MS with COPD. Based on GLP-1, it is proposed to create a drug to stimulate the regeneration of endothelium damaged in MS and COPD. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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15 pages, 1848 KiB  
Article
Effects of Arachidonic and Docosohexahenoic Acid Supplementation during Gestation in Rats. Implication of Placental Oxidative Stress
by Cynthia Guadalupe Reyes-Hernández, David Ramiro-Cortijo, Pilar Rodríguez-Rodríguez, Sonia Giambelluca, Manuela Simonato, Mª del Carmen González, Angel Luis López de Pablo, Mª del Rosario López-Giménez, Paola Cogo, Miguel Sáenz de Pipaón, Virgilio P. Carnielli and Silvia M. Arribas
Int. J. Mol. Sci. 2018, 19(12), 3863; https://doi.org/10.3390/ijms19123863 - 4 Dec 2018
Cited by 13 | Viewed by 4110
Abstract
Arachidonic and docosahexaenoic acids (ARA and DHA) are important during pregnancy. However, the effects of dietary supplementation on fetal growth and oxidative stress are inconclusive. We aimed to assess the effect of high ARA and DHA diet during rat gestation on: (1) ARA [...] Read more.
Arachidonic and docosahexaenoic acids (ARA and DHA) are important during pregnancy. However, the effects of dietary supplementation on fetal growth and oxidative stress are inconclusive. We aimed to assess the effect of high ARA and DHA diet during rat gestation on: (1) ARA and DHA availability in plasma and placenta, (2) fetal growth, and (3) placental oxidative stress, analyzing the influence of sex. Experimental diet (ED) was prepared by substituting soybean oil in the control diet (CD) by a fungi/algae-based oil containing ARA and DHA (2:1). Rats were fed with CD or ED during gestation; plasma, placenta, and fetuses were obtained at gestational day 20. DHA, ARA, and their precursors were analyzed in maternal plasma and placenta by gas chromatography/mass spectrophotometry. Fetuses and placentas were weighed, the proportion of fetuses with intrauterine growth restriction (IUGR) determined, and placental lipid and protein oxidation analyzed. ED fetuses exhibited lower body weight compared to CD, being >40% IUGR; fetal weight negatively correlated with maternal plasma ARA, but not DHA. Only ED female placenta exhibited higher lipid and protein oxidation compared to its CD counterparts; lipid peroxidation is negatively associated with fetal weight. In conclusion, high ARA during gestation associates with IUGR, through placental oxidative stress, with females being more susceptible. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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15 pages, 8065 KiB  
Article
MiR-205 Mediated Cu-Induced Lipid Accumulation in Yellow Catfish Pelteobagrus fulvidraco
by Heng-Yang Cui, Qi-Liang Chen, Xiao-Ying Tan, Dian-Guang Zhang, Shi-Cheng Ling, Guang-Hui Chen and Zhi Luo
Int. J. Mol. Sci. 2018, 19(10), 2980; https://doi.org/10.3390/ijms19102980 - 29 Sep 2018
Cited by 17 | Viewed by 3337
Abstract
The present working hypothesis is that the Cu-induced changes in lipid metabolism may be mediated by miRNAs. Here, we describe the miRNA profile of the liver tissues of yellow catfish exposed to waterborne Cu, based on larger-scale sequencing of small RNA libraries. We [...] Read more.
The present working hypothesis is that the Cu-induced changes in lipid metabolism may be mediated by miRNAs. Here, we describe the miRNA profile of the liver tissues of yellow catfish exposed to waterborne Cu, based on larger-scale sequencing of small RNA libraries. We identified a total of 172 distinct miRNAs. Among these miRNAs, compared to the control, mRNA expression levels of 16 miRNAs (miR-203a, 205, 1788-3p, 375, 31, 196a, 203b-3p, 2187-5p, 196d, 459-3p, 153a and miR-725, and two novel-miRNAs: chr4-1432, chr-7684) were down-regulated, and mRNA levels of miR-212 and chr20-5274 were up-regulated in Cu-exposed group. The functions of their target genes mainly involved ether lipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism and α-linolenic acid metabolism. Cu exposure inhibited the expression of miR-205, whose predicted target genes were enriched in the pathway of lipid metabolism, including fas, lxrα, ddit3, lamp2, casp3a and baxa. These potential target genes were further verified by Dual-luciferase reporter gene assay. Using primary hepatocytes of yellow catfish, Cu incubation down-regulated miR-205 expression, and increased TG contents and FAS activity. LXR antagonist effectively ameliorate the Cu-induced change of TG content and FAS activity. These data suggest that down-regulation of the miRNA-205 may be an important step in Cu-induced changes in lipid metabolism in yellow catfish. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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Review

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22 pages, 500 KiB  
Review
Molecular Mechanisms Responsible for Diastolic Dysfunction in Diabetes Mellitus Patients
by Jovana Nikolajević Starčević, Miodrag Janić and Mišo Šabovič
Int. J. Mol. Sci. 2019, 20(5), 1197; https://doi.org/10.3390/ijms20051197 - 9 Mar 2019
Cited by 35 | Viewed by 5706
Abstract
In diabetic patients, cardiomyopathy is an important cause of heart failure, but its pathophysiology has not been completely understood thus far. Myocardial hypertrophy and diastolic dysfunction have been considered the hallmarks of diabetic cardiomyopathy (DCM), while systolic function is affected in the latter [...] Read more.
In diabetic patients, cardiomyopathy is an important cause of heart failure, but its pathophysiology has not been completely understood thus far. Myocardial hypertrophy and diastolic dysfunction have been considered the hallmarks of diabetic cardiomyopathy (DCM), while systolic function is affected in the latter stages of the disease. In this article we propose the potential pathophysiological mechanisms responsible for myocardial hypertrophy and increased myocardial stiffness leading to diastolic dysfunction in this specific entity. According to our model, increased myocardial stiffness results from both cellular and extracellular matrix stiffness as well as cell–matrix interactions. Increased intrinsic cardiomyocyte stiffness is probably the most important contributor to myocardial stiffness. It results from the impairment in cardiomyocyte cytoskeleton. Several other mechanisms, specifically affected by diabetes, seem to also be significantly involved in myocardial stiffening, i.e., impairment in the myocardial nitric oxide (NO) pathway, coronary microvascular dysfunction, increased inflammation and oxidative stress, and myocardial sodium glucose cotransporter-2 (SGLT-2)-mediated effects. Better understanding of the complex pathophysiology of DCM suggests the possible value of drugs targeting the listed mechanisms. Antidiabetic drugs, NO-stimulating agents, anti-inflammatory agents, and SGLT-2 inhibitors are emerging as potential treatment options for DCM. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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18 pages, 1427 KiB  
Review
Obesity, DNA Damage, and Development of Obesity-Related Diseases
by Marta Włodarczyk and Grażyna Nowicka
Int. J. Mol. Sci. 2019, 20(5), 1146; https://doi.org/10.3390/ijms20051146 - 6 Mar 2019
Cited by 155 | Viewed by 13691
Abstract
Obesity has been recognized to increase the risk of such diseases as cardiovascular diseases, diabetes, and cancer. It indicates that obesity can impact genome stability. Oxidative stress and inflammation, commonly occurring in obesity, can induce DNA damage and inhibit DNA repair mechanisms. Accumulation [...] Read more.
Obesity has been recognized to increase the risk of such diseases as cardiovascular diseases, diabetes, and cancer. It indicates that obesity can impact genome stability. Oxidative stress and inflammation, commonly occurring in obesity, can induce DNA damage and inhibit DNA repair mechanisms. Accumulation of DNA damage can lead to an enhanced mutation rate and can alter gene expression resulting in disturbances in cell metabolism. Obesity-associated DNA damage can promote cancer growth by favoring cancer cell proliferation and migration, and resistance to apoptosis. Estimation of the DNA damage and/or disturbances in DNA repair could be potentially useful in the risk assessment and prevention of obesity-associated metabolic disorders as well as cancers. DNA damage in people with obesity appears to be reversible and both weight loss and improvement of dietary habits and diet composition can affect genome stability. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disorders)
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