Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
Front Endocrinol (Lausanne). 2022 Feb 22;13:828780. doi: 10.3389/fendo.2022.828780. eCollection 2022.
Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.
性激素导致男性和女性在体脂分布和相关疾病风险方面存在差异。雌激素浓度较高与女性化的身体形态相关，臀部和大腿的脂肪储存较多，而内脏脂肪储存较少。雌激素对内脏脂肪的保护作用在绝经后雌激素水平较低的女性中表现出来，激素替代疗法治疗后观察到的中心性体脂减少也表现出这种作用。雌激素在靶细胞中通过雌激素受体（ERα、ERβ 和 GPR30）发挥其生理作用，包括脂肪细胞。在肥胖发生之前，研究表明雌激素还可以预防脂肪炎症和纤维化。雌激素依赖性体脂分布的机制尚不完全清楚，但涉及例如增加 mTOR 信号传导以及抑制自噬和脂肪生成/脂质储存。雌激素通过与重塑 DNA 甲基化和组蛋白尾部翻译后修饰的酶相互作用，在脂肪生成基因的表观遗传调控中发挥关键作用。然而，还需要更多的研究来绘制 ER 在不同脂肪细胞亚型（包括皮下和内脏脂肪组织中的亚型）中的差异表观遗传作用图谱。我们在此综述了 ER 介导的脂肪细胞中转录和表观遗传调控的最新发现，这些发现可以解释体脂分布和肥胖相关疾病风险的性别二态性。
