Chronic stress, epigenetics, and adipose tissue metabolism in the obese state
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REVIEW
Chronic stress, epigenetics, and adipose tissue metabolism in the obese state Yang Xiao1, Dongmin Liu2, Mark A. Cline1,3 and Elizabeth R. Gilbert1,3*
Abstract In obesity, endocrine and metabolic perturbations, including those induced by chronic activation of the hypothalamus–pituitary–adrenal axis, are associated with the accumulation of adipose tissue and inflammation. Such changes are attributable to a combination of genetic and epigenetic factors that are influenced by the environment and exacerbated by chronic activation of the hypothalamus–pituitary–adrenal axis. Stress exposure at different life stages can alter adipose tissue metabolism directly through epigenetic modification or indirectly through the manipulation of hypothalamic appetite regulation, and thereby contribute to endocrine changes that further disrupt whole-body energy balance. This review synthesizes current knowledge, with an emphasis on human clinical trials, to describe metabolic changes in adipose tissue and associated endocrine, genetic and epigenetic changes in the obese state. In particular, we discuss epigenetic changes induced by stress exposure and their contribution to appetite and adipocyte dysfunction, which collectively promote the pathogenesis of obesity. Such knowledge is critical for providing future directions of metabolism research and targets for treating metabolic disorders. Keywords: Adipose tissue, Obesity, Stress, Epigenetics, Metabolism, Nutrition Introduction Adipose tissue, in addition to providing a reservoir of energy, serves as an endocrine organ, as it synthesizes and secretes a diverse array of hormones and cytokines that regulate metabolic homeostasis and control various physiological functions such as energy metabolism, thermoregulation, food intake, and glucose homeostasis [1–3]. There are two major types of adipose tissue—white adipose tissue (WAT), which is mainly composed of white adipocytes that are designed for energy storage, and brown adipose tissue (BAT), containing brown adipocytes that largely function to dissipate energy in the form of heat during non-shivering thermogenesis [4]. More recently, a third type of adipocyte—beige (also called brite/inducible BAT), was found to arise in WAT *Correspondence: [email protected] 1 Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA Full list of author information is available at the end of the article
in response to various cues such as chronic cold exposure and sympathomimetic treatments, with thermoregulatory and energy balance functions [5]. WAT is distributed throughout the body mainly in the subcutaneous (sWAT), visceral (vWAT), inter- (itMAT) and intramuscular (iMAT) as well as bone marrow (MAT) depots [6], among which sWAT and vWAT are of the most metabolic importance. sWAT emerges prior to vWAT during embryonic development [7]. sWAT is located underneath the skin and is primarily responsible for energy storage [8]. In humans, about 80% of body adipose tissue is sWA
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