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.

中文翻译：

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肥胖状态下的慢性应激，表观遗传学和脂肪组织代谢

在肥胖症中，内分泌和代谢紊乱（包括下丘脑-垂体-肾上腺轴的慢性激活引起的紊乱）与脂肪组织的积累和炎症有关。这种变化归因于遗传和表观遗传因素的组合，这些因素受到环境的影响，并由于下丘脑-垂体-肾上腺轴的慢性激活而加剧。处于不同生命阶段的压力暴露可直接通过表观遗传修饰或通过操纵下丘脑食欲调节间接改变脂肪组织的代谢，从而促进内分泌变化，从而进一步破坏全身能量平衡。这篇评论综合了当前的知识，重点是人体临床试验，描述肥胖状态下脂肪组织的代谢变化以及相关的内分泌，遗传和表观遗传变化。特别是，我们讨论了应激暴露引起的表观遗传变化及其对食欲和脂肪细胞功能障碍的贡献，这些共同促进了肥胖的发病机理。这些知识对于提供新的代谢研究方向和治疗代谢异常的目标至关重要。