scholarly journals Molecular Insight into the Interaction between Epigenetics and Leptin in Metabolic Disorders

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1872 ◽  
Author(s):  
Adam Wróblewski ◽  
Justyna Strycharz ◽  
Ewa Świderska ◽  
Karolina Drewniak ◽  
Józef Drzewoski ◽  
...  

Nowadays, it is well-known that the deregulation of epigenetic machinery is a common biological event leading to the development and progression of metabolic disorders. Moreover, the expression level and actions of leptin, a vast adipocytokine regulating energy metabolism, appear to be strongly associated with epigenetics. Therefore, the aim of this review was to summarize the current knowledge of the epigenetic regulation of leptin as well as the leptin-induced epigenetic modifications in metabolic disorders and associated phenomena. The collected data indicated that the deregulation of leptin expression and secretion that occurs during the course of metabolic diseases is underlain by a variation in the level of promoter methylation, the occurrence of histone modifications, along with miRNA interference. Furthermore, leptin was proven to epigenetically regulate several miRNAs and affect the activity of the histone deacetylases. These epigenetic modifications were observed in obesity, gestational diabetes, metabolic syndrome and concerned various molecular processes like glucose metabolism, insulin sensitivity, liver fibrosis, obesity-related carcinogenesis, adipogenesis or fetal/early postnatal programming. Moreover, the circulating miRNA profiles were associated with the plasma leptin level in metabolic syndrome, and miRNAs were found to be involved in hypothalamic leptin sensitivity. In summary, the evidence suggests that leptin is both a target and a mediator of epigenetic changes that develop in numerous tissues during metabolic disorders.

2019 ◽  
Vol 9 (5-s) ◽  
pp. 167-169
Author(s):  
Dhananjay S. Khot

The metabolic disorders are major health issues of today’s scenario and incidences of metabolic diseases increases day by day due to the disturbed pattern of life style. Ayurveda texts have described term “Santarpanjanya Vikaras” which resembles diseases of defective tissue metabolism. Ayurveda mentioned that improper dietary habits and sedentary life style affects state of Agni which resulted Ama production and finally leading to the metabolic syndrome. The vitiation of Dosha, diminish state of Dhatu and blockage of channels, etc. also can initiate pathogenesis of metabolic disorders. The Kayachikitsa branch of Ayurveda recommended use of internal medicine for the management of various metabolic disorders. Considering increased health burden of society due to the metabolic syndrome present article explore role of ayurveda internal medicine for the management of metabolic syndrome. Keywords: Ayurveda, metabolic syndrome, Santarpanjanya, Madhumeha and Sthoulya.       


2020 ◽  
Vol 43 (10) ◽  
pp. 1373-1389 ◽  
Author(s):  
R. Spinelli ◽  
L. Parrillo ◽  
M. Longo ◽  
P. Florese ◽  
A. Desiderio ◽  
...  

Abstract Aim Over the last decades, the shift in age distribution towards older ages and the progressive ageing which has occurred in most populations have been paralleled by a global epidemic of obesity and its related metabolic disorders, primarily, type 2 diabetes (T2D). Dysfunction of the adipose tissue (AT) is widely recognized as a significant hallmark of the ageing process that, in turn, results in systemic metabolic alterations. These include insulin resistance, accumulation of ectopic lipids and chronic inflammation, which are responsible for an elevated risk of obesity and T2D onset associated to ageing. On the other hand, obesity and T2D, the paradigms of AT dysfunction, share many physiological characteristics with the ageing process, such as an increased burden of senescent cells and epigenetic alterations. Thus, these chronic metabolic disorders may represent a state of accelerated ageing. Materials and methods A more precise explanation of the fundamental ageing mechanisms that occur in AT and a deeper understanding of their role in the interplay between accelerated ageing and AT dysfunction can be a fundamental leap towards novel therapies that address the causes, not just the symptoms, of obesity and T2D, utilizing strategies that target either senescent cells or DNA methylation. Results In this review, we summarize the current knowledge of the pathways that lead to AT dysfunction in the chronological ageing process as well as the pathophysiology of obesity and T2D, emphasizing the critical role of cellular senescence and DNA methylation. Conclusion Finally, we highlight the need for further research focused on targeting these mechanisms.


2018 ◽  
Vol 24 (15) ◽  
pp. 1711-1716 ◽  
Author(s):  
Elena V. Galitsyna ◽  
Andrey V. Zhelankin ◽  
Igor A. Sobenin ◽  
Alexander N. Orekhov

In addition to external factors, such as exercise, food and the environment, genetic predisposition makes great contribution to the development of metabolic disorders and cardiovascular disease. This review is aimed to examine the genetic basis of complex metabolic disorders conventionally described as "metabolic syndrome" (MetS), with the special focus on currently known mutations in the nuclear and mitochondrial genomes, which are associated with both the individual components of MetS and combinations thereof, and also on the studies of the relationship of MetS phenotype as a binary trait. The defects in the mitochondrial genome should be considered as one of the possible genetic reasons leading to MetS. It is known that mitochondrial dysfunction is closely associated with metabolic disorders, as mitochondria are the center of energy metabolism. Consequently, the changes in mitochondrial genes and their functions affect regulation of metabolism. Until now, the role of mitochondrial DNA damage in the development of cardiovascular diseases, age-related and metabolic disorders is still poorly understood. The results of performed studies would help assessing the role of mitochondrial DNA mutations in susceptibility to metabolic syndrome and related metabolic diseases.


2021 ◽  
Author(s):  
Tatsuya Kondo ◽  
Nobukazu Miyakawa ◽  
Sayaka Kitano ◽  
Takuro Watanabe ◽  
Rieko Goto ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities, but is deteriorated by chronic metabolic insults. Heat shock (HS) with appropriate mild electrical stimulation (MES) activates HSR, and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (2 times/week, n=10), patients with metabolic syndrome (4 times/week, n=40), and patients with T2DM (n=100; 4 times/week (n=40) and 2, 4, 7 times/week (n=20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1158 ◽  
Author(s):  
Yolanda Gálvez-Ontiveros ◽  
Sara Páez ◽  
Celia Monteagudo ◽  
Ana Rivas

Endocrine disruptors (EDCs) have been associated with the increased incidence of metabolic disorders. In this work, we conducted a systematic review of the literature in order to identify the current knowledge of the interactions between EDCs in food, the gut microbiota, and metabolic disorders in order to shed light on this complex triad. Exposure to EDCs induces a series of changes including microbial dysbiosis and the induction of xenobiotic pathways and associated genes, enzymes, and metabolites involved in EDC metabolism. The products and by-products released following the microbial metabolism of EDCs can be taken up by the host; therefore, changes in the composition of the microbiota and in the production of microbial metabolites could have a major impact on host metabolism and the development of diseases. The remediation of EDC-induced changes in the gut microbiota might represent an alternative course for the treatment and prevention of metabolic diseases.


2020 ◽  
Vol 20 (1) ◽  
pp. 9-22
Author(s):  
Sergey A. Apryatin ◽  
Marina N. Karpenko ◽  
Zamira M. Muruzheva ◽  
Maria V. Bolshakova ◽  
Daria N. Magazenkova ◽  
...  

The aim of the study is the modern scientific literature estimation in the field of the investigation of neurodegenerative and metabolic disorders mediated by the trace amines and their receptors. The analysis of modern ideas about the feedback of neurodegenerative and metabolic diseases in which the trace amines and their receptors are involved was carried out. The important role of trace amines and their receptors in the regulation of the dopamine system, in connection with metabolic and neurodegenerative diseases, including Parkinsons disease, ADHD, schizophrenia, obesity, metabolic syndrome and other pathological conditions, has been shown. Trace amines and their receptors have a direct effect on dopamine systems, being regulators of various metabolic and neurodegenerative processes, participating in energy metabolism, neurogenesis, and other vital processes.


2019 ◽  
Vol 20 (6) ◽  
pp. 419-427 ◽  
Author(s):  
Ezgi Şanlı ◽  
Seray Kabaran

Background: Maternal obesity and maternal overnutrition, can lead to epigenetic alterations during pregnancy and these alterations can influence fetal and neonatal phenotype which increase the risk of metabolic disorders in later stages of life. Objective: The effects of maternal obesity on fetal programming and potential mechanisms of maternal epigenetic regulation of gene expression which have persistent effects on fetal health and development were investigated. Method: Review of the literature was carried out in order to discuss the effects of maternal obesity and epigenetic mechanisms in fetal programming of metabolic disorders. All abstracts and full-text articles were examined and the most relevant articles were included in this review. Results: Maternal obesity and maternal overnutrition during fetal period has important overall effects on long-term health. Maternal metabolic alterations during early stages of fetal development can lead to permanent changes in organ structures, cell numbers and metabolism. Epigenetic modifications (DNA methylation, histone modifications, microRNAs) play an important role in disease susceptibility in the later stages of human life. Maternal nutrition alter expression of hypothalamic genes which can increase fetal and neonatal energy intake. Epigenetic modifications may affect the increasing rate of obesity and other metabolic disorders worldwide since the impact of these changes can be passed through generations. Conclusion: Weight management before and during pregnancy, together with healthy nutritional intakes may improve the maternal metabolic environment, which can reduce the risks of fetal programming of metabolic diseases. Further evidence from long-term follow-up studies are needed in order to determine the role of maternal obesity on epigenetic mechanisms.


2018 ◽  
Vol 24 (23) ◽  
pp. 2729-2742 ◽  
Author(s):  
Nasrin Sharifi ◽  
Reza Tabrizi ◽  
Mahmood Moosazadeh ◽  
Naghmeh Mirhosseini ◽  
Kamran B. Lankarani ◽  
...  

Background and objective: Oxidative stress and inflammation are key parameters in developing metabolic disorders. Hence, antioxidant intake might be an appropriate approach. Several studies have evaluated the effect of coenzyme Q10 (CoQ10) supplementation on lipid profile among patients with metabolic diseases, though findings are controversial. The aim of this systematic review and meta-analysis was to determine the effects of CoQ10 supplementation on lipid profile in patients with metabolic disorders. Methods: We searched PubMed, EMBASE, Web of Science and Cochrane Library databases until July 2017. Prospective clinical trials were selected assessing the effect of CoQ10 supplementation on different biomarkers. Two reviewers independently assessed the eligibility of studies, extracted data, and evaluated the risk of bias of included studies. A fixed- or random-effects model was used to pool the data, which expressed as a standardized mean difference with 95% confidence interval. Heterogeneity was measured using a Q-test and with I2 statistics. Results: A total of twenty-one controlled trials (514 patients and 525 controls) were included. The meta-analysis indicated a significant reduction in serum triglycerides levels (SMD -0.28; 95% CI, -0.56, -0.005). CoQ10 supplementation also decreased total-cholesterol (SMD -0.07; 95% CI, -0.45, 0.31), increased LDL- (SMD 0.04; 95% CI, -0.27, 0.36), and HDL-cholesterol levels (SMD 0.10; 95% CI, -0.32, 0.51), not statistically significant. Conclusion: CoQ10 supplementation may significantly reduce serum triglycerides levels, and help to improve lipid profiles in patients with metabolic disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.


2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Isabell Kaczmarek ◽  
Tomáš Suchý ◽  
Simone Prömel ◽  
Torsten Schöneberg ◽  
Ines Liebscher ◽  
...  

Abstract G protein-coupled receptors (GPCRs) modulate a variety of physiological functions and have been proven to be outstanding drug targets. However, approximately one-third of all non-olfactory GPCRs are still orphans in respect to their signal transduction and physiological functions. Receptors of the class of Adhesion GPCRs (aGPCRs) are among these orphan receptors. They are characterized by unique features in their structure and tissue-specific expression, which yields them interesting candidates for deorphanization and testing as potential therapeutic targets. Capable of G-protein coupling and non-G protein-mediated function, aGPCRs may extend our repertoire of influencing physiological function. Besides their described significance in the immune and central nervous systems, growing evidence indicates a high importance of these receptors in metabolic tissue. RNAseq analyses revealed high expression of several aGPCRs in pancreatic islets, adipose tissue, liver, and intestine but also in neurons governing food intake. In this review, we focus on aGPCRs and their function in regulating metabolic pathways. Based on current knowledge, this receptor class represents high potential for future pharmacological approaches addressing obesity and other metabolic diseases.


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