Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy.
Nat Commun. 2021 Nov 25;12(1):6883. doi: 10.1038/s41467-021-27272-x.
In female mammals, the cessation of ovarian functions is associated with significant metabolic alterations, weight gain, and increased susceptibility to a number of pathologies associated with ageing. The molecular mechanisms triggering these systemic events are unknown because most tissues are responsive to lowered circulating sex steroids. As it has been demonstrated that isoform alpha of the estrogen receptor (ERα) may be activated by both estrogens and amino acids, we test the metabolic effects of a diet enriched in specific amino acids in ovariectomized (OVX) mice. This diet is able to block the OVX-induced weight gain and fat deposition in the liver. The use of liver-specific ERα KO mice demonstrates that the hepatic ERα, through the control of liver lipid metabolism, has a key role in the systemic response to OVX. The study suggests that the liver ERα might be a valuable target for dietary treatments for the post-menopause.
在雌性哺乳动物中，卵巢功能的停止与显著的代谢改变、体重增加以及对许多与衰老相关的病理状态的易感性增加有关。触发这些全身事件的分子机制尚不清楚，因为大多数组织对循环性激素水平降低有反应。由于已经证明雌激素受体 (ERα) 的同工型 alpha 可以被雌激素和氨基酸激活，我们测试了富含特定氨基酸的饮食对去卵巢 (OVX) 小鼠的代谢影响。这种饮食能够阻止 OVX 引起的体重增加和肝脏脂肪沉积。使用肝脏特异性 ERα KO 小鼠表明，肝脏 ERα 通过控制肝脏脂质代谢，在 OVX 引起的全身反应中起着关键作用。该研究表明，肝脏 ERα 可能是绝经后饮食治疗的一个有价值的靶点。
