Adiponectin Related Vascular and Cardiac Benefits in Obesity: Is There a Role for an Epigenetically Regulated Mechanism?

Abstract

In obesity, several epigenetic modifications, including histones remodeling, DNA methylation, and microRNAs, could accumulate and determine increased expression of inflammatory molecules, the adipokines, that in turn might induce or accelerate the onset and development of cardiovascular and metabolic disorders. In order to better clarify the potential epigenetic mechanisms underlying the modulation of the inflammatory response by adipokines, the DNA methylation profile in peripheral leukocytes of the promoter region of IL-6 and NF-kB genes and plasma miRNA-21 levels were evaluated in 356 healthy subjects, using quantitative pyrosequencing-based analysis, and correlated with plasma adiponectin levels, body fat content and the primary pro-inflammatory markers. In addition, correlation analysis of DNA methylation profiles and miRNA-21 plasma levels with intima-media thickness (IMT), a surrogate marker for early atherosclerosis, left ventricular mass (LVM), left ventricular ejection fraction (LVEF), and cardiac performance index (MPI) was also performed to evaluate any potential clinical implication in terms of cardiovascular outcome. Results achieved confirmed the role of epigenetics in the obesity-related cardiovascular complications and firstly supported the potential role of plasma miRNA-21 and IL-6 and NF-kB DNA methylation changes in nucleated blood cells as potential biomarkers for predicting cardiovascular risk in obesity. Furthermore, our results, showing a role of adiponectin in preventing epigenetic modification induced by increased adipose tissue content in obese subjects, provide new evidence of an additional mechanism underlying the anti-inflammatory properties and the cardiovascular benefits of adiponectin. The exact mechanisms underlying the obesity-related epigenetic modifications found in the blood cells and whether similar epigenetic changes reflect adipose and myocardial tissue modifications need to be further investigated in future experiments.

Dual Roles of Coconut Oil and Its Major Component Lauric Acid on Redox Nexus: Focus on Cytoprotection and Cancer Cell Death

“…On the other hand, Macrophages and lymphocytes secrete TNFα in response to cell damage. Our observation is concomitant to previous studies where IL6 and TNFα were found to be elevated in patients with lipid abnormalities and insulin resistance ( Pickup et al, 1997 ; Bahceci et al, 2007 ; Popko et al, 2010 ; Fontanella et al, 2021 ).…”

Matr3 reshapes m6A modification complex to alleviate macrophage inflammation during atherosclerosis

“…Up to now, many risk factors are reported to contribute to atherosclerosis, including smoking, hypercholesterolemia, hypertension, hyperglycemia, genetic factors, and epigenetic factors [11][12][13][14]. The N6-methyladenosine (m6A) modi cation is the most abundant epi-transcriptomic modi cation in mRNA, and plays important roles in various diseases, such as obesity, cancers, hypertension and viral infection through regulating RNA stability, export, splicing or translation [15,16].…”

Organokines in Rheumatoid Arthritis: A Critical Review

“…Age, stage of the disease, and several other factors influence the levels of OPG, justifying such discrepant results between studies. Furthermore, autoantibodies to osteoprotegerin are associated with increased bone resorption in RA, with OPG antibody-positive patients having longer disease duration and activity and higher levels of bone resorption markers [ 66 , 67 , 70 , 71 , 72 ].…”

“…In musculoskeletal disorders such as RA, adipokines were described as modulators of bones, synovial membranes, and cartilages activities. Additionally, higher levels of adipokines are encountered in both serum and synovial fluid in patients with RA than in those who are healthy [ 6 , 7 , 72 , 74 ].…”