Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.
Pharmacol Ther. 2016 May;161:52-66. doi: 10.1016/j.pharmthera.2016.03.005. Epub 2016 Mar 22.
Uncorrected obesity has been associated with cardiac hypertrophy and contractile dysfunction. Several mechanisms for this cardiomyopathy have been identified, including oxidative stress, autophagy, adrenergic and renin-angiotensin aldosterone overflow. Another process that may regulate effects of obesity is epigenetics, which refers to the heritable alterations in gene expression or cellular phenotype that are not encoded on the DNA sequence. Advances in epigenome profiling have greatly improved the understanding of the epigenome in obesity, where environmental exposures during early life result in an increased health risk later on in life. Several mechanisms, including histone modification, DNA methylation and non-coding RNAs, have been reported in obesity and can cause transcriptional suppression or activation, depending on the location within the gene, contributing to obesity-induced complications. Through epigenetic modifications, the fetus may be prone to detrimental insults, leading to cardiac sequelae later in life. Important links between epigenetics and obesity include nutrition, exercise, adiposity, inflammation, insulin sensitivity and hepatic steatosis. Genome-wide studies have identified altered DNA methylation patterns in pancreatic islets, skeletal muscle and adipose tissues from obese subjects compared with non-obese controls. In addition, aging and intrauterine environment are associated with differential DNA methylation. Given the intense research on the molecular mechanisms of the etiology of obesity and its complications, this review will provide insights into the current understanding of epigenetics and pharmacological and non-pharmacological (such as exercise) interventions targeting epigenetics as they relate to treatment of obesity and its complications. Particular focus will be on DNA methylation, histone modification and non-coding RNAs.
未经校正的肥胖与心脏肥大和收缩功能障碍有关。已经确定了这种心肌病的几种机制，包括氧化应激、自噬、肾上腺素能和肾素-血管紧张素-醛固酮溢出。另一个可能调节肥胖影响的过程是表观遗传学，它是指基因表达或细胞表型的可遗传改变，而这些改变不在 DNA 序列上编码。表观基因组谱分析的进展极大地提高了人们对肥胖症中表观基因组的理解，即在生命早期的环境暴露导致生命后期健康风险增加。已经在肥胖症中报道了几种机制，包括组蛋白修饰、DNA 甲基化和非编码 RNA，它们可以根据基因内的位置导致转录抑制或激活，导致肥胖引起的并发症。通过表观遗传修饰，胎儿可能容易受到有害刺激，导致以后的心脏后遗症。表观遗传学和肥胖之间的重要联系包括营养、运动、肥胖、炎症、胰岛素敏感性和肝脂肪变性。全基因组研究已经在肥胖症患者的胰腺胰岛、骨骼肌和脂肪组织中发现了与非肥胖对照组相比改变的 DNA 甲基化模式。此外，衰老和宫内环境与差异 DNA 甲基化有关。鉴于对肥胖及其并发症病因的分子机制的深入研究，本综述将深入了解表观遗传学以及针对表观遗传学的药理学和非药理学（如运动）干预措施，因为它们与肥胖及其并发症的治疗有关。特别关注 DNA 甲基化、组蛋白修饰和非编码 RNA。
