Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

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.

The Potential Role of Exosomes in Child and Adolescent Obesity

“…Among them, leptin (LEP), a peptide hormone mainly released from WAT, mediates a complex communication between the intestine, adipose tissue and the brain, leading to reduced food consumption and enhanced energy expenditure, thus regulating body weight homeostasis [ 46 ]. Even though the increase of adipose tissue mass in obesity increases production of leptin, soluble leptin receptors (LEPRs, the main leptin binding proteins in circulation that result from LEPR cleavage and regulate leptin function and bioavailability) decrease, while leptin transport into the central nervous system (CNS) is not commensurately increased, resulting in decreased hypothalamic leptin signaling, increased leptin levels and leptin resistance [ 47 , 48 , 49 , 50 ]. Adiponectin, another adipocyte-specific hormone, actually the most abundant adipocytokine in plasma and ubiquitously expressed in adipose tissue [ 10 ], displays anti-inflammatory and antifibrotic properties in many organs [ 51 , 52 , 53 ].…”

“…Chronic hypersecretion of stress mediators, such as glucocorticoids, may result in insulin and leptin hypersecretion, contributing to insulin and leptin resistance, along with dysregulation of appetite and food intake by inducing alterations in the reward system, finally leading to obesity [ 86 ]. Also, overexpression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) resulting in increased conversion to active cortisol, has been associated with central obesity because of increased activity in the adipose tissue of obese adult females [ 48 ]. Importantly, the offspring of obese mothers display a higher baseline cortisol, resulting in a dysregulated stress response and predisposition to metabolic dysfunction [ 48 ].…”

“…Also, overexpression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) resulting in increased conversion to active cortisol, has been associated with central obesity because of increased activity in the adipose tissue of obese adult females [ 48 ]. Importantly, the offspring of obese mothers display a higher baseline cortisol, resulting in a dysregulated stress response and predisposition to metabolic dysfunction [ 48 ].…”

“…There are rapid, dynamic and reversible or long-term less reversible adaptive alterations of genome activity without concurrent changes in the DNA sequence, following environmental stimuli [ 87 ]. Environmental factors, including nutrition, physical activity, lifestyle, sleep habits, chronic stress, pollutants and so forth, can trigger the onset of obesity by epigenetically modifying genes involved in multiple biological processes in metabolism and immunity [ 48 ]. Epigenetic changes may occur during fetal life, early childhood, and adolescence and to a lesser degree, in adulthood, and encompass DNA methylation, glycosylation, myristoylation, post-translational histone modifications, as well as nc RNAs orchestrating a variety of cellular processes, including gene expression [ 88 ].…”

Obesity and chronic kidney disease: prevalence, mechanism, and management

“…A r t i c l e (45)(46)(47)(48) Increased podocyte injury (29) Glomerulomegaly & glomerulosclerosis (29) Excessive tubular sodium reabsorption (49)(50)(51) Increased sympathetic activity (29) Increased RAAS activity (47,51) Metabolic effects Abnormal lipid metabolism (52,53,73) Adipokine dysregulation (54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(66)(67)(68)(69) Increased insulin resistance (64,65) Increased inflammation (70,71,73) Increased oxidative stress (73,74) Lipid nephrotoxicity Excessive renal fat accumulation (70)(71)(72) Glomerular and tubular cell injuries (71)(72)(73) Mitochondrial dysfunction, oxidative stress & inflammation (71,73,74) Increased FFA toxicity to proximal tubu...…”