This review focuses on the human genetics, epidemiology, and molecular pathophysiology of sex differences in central obesity, adipose distribution, and related cardiometabolic disorders. Distribution of fat is important for cardiometabolic health, with peripheral fat depots having a protective effect and central visceral fat depots conferring a detrimental effect on health. There are important sex differences in fat distribution that are masked when studying body mass index as a measure of obesity. From epidemiological, murine, and in vitro studies, several mechanisms have been proposed to explain the sex differences in adipose distribution, including sex hormonal effects, cell-intrinsic properties, and the microenvironment in fat depots. More recently, human genetics have revealed hundreds of loci for central obesity providing disruptive opportunities for mechanistic discoveries and clinical translation. A striking feature is that over one-third of these loci have reproducible but poorly understood sexual dimorphic associations with central obesity, most having stronger effects in women. Understanding the genetic and molecular mechanisms of adipose distribution and its sexual dimorphism in humans provides a unique opportunity to promote the use of precision medicine for early identification of at-risk individuals, and the development of novel therapeutic strategies for central obesity and related cardiometabolic disorders.

中文翻译：

---

脂肪分布和相关的心脏代谢紊乱的基因组驱动因素中的性别差异：精密医学的机会。

这篇综述着重于人类遗传学，流行病学和中枢性肥胖，脂肪分布以及相关的心脏代谢紊乱的性别差异的分子病理生理学。脂肪的分布对于心脏代谢的健康很重要，外围的脂肪库具有保护作用，而中央内脏的脂肪库对健康有不利影响。研究体重指数以衡量肥胖时，脂肪分布中存在重要的性别差异，这些差异被掩盖了。从流行病学，鼠类和体外研究中，已经提出了几种机制来解释脂肪分布中的性别差异，包括性激素作用，细胞内在特性和脂肪库中的微环境。最近，人类遗传学揭示了数百个肥胖中心点，为机械发现和临床翻译提供了破坏性的机会。一个显着的特征是，这些基因座中有超过三分之一具有可重现的但对中型肥胖的二态性相关性了解甚少，大多数对女性的影响更大。了解人类中脂肪分布及其性二态性的遗传和分子机制，为促进使用精密医学来早期识别高危人群以及开发针对中枢性肥胖症和相关的心脏代谢异常的新型治疗策略提供了独特的机会。一个显着的特征是，这些基因座中有超过三分之一具有可重现的但对中型肥胖的二态性相关性了解甚少，大多数对女性的影响更大。了解人类中脂肪分布及其性二态性的遗传和分子机制，为促进使用精密医学来早期识别高危人群提供了独特的机会，并为中枢性肥胖症和相关的心脏代谢紊乱开发了新的治疗策略。一个显着的特征是，这些基因座中有超过三分之一具有可重现的但对中型肥胖的二态性相关性了解甚少，大多数对女性的影响更大。了解人类中脂肪分布及其性二态性的遗传和分子机制，为促进使用精密医学来早期识别高危人群提供了独特的机会，并为中枢性肥胖症和相关的心脏代谢紊乱开发了新的治疗策略。