Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, New York City, NY, USA.
Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, New York City, NY, USA.
Life Sci Alliance. 2022 Aug 25;5(11). doi: 10.26508/lsa.202201502. Print 2022 Nov.
Hyperphagia and obesity profoundly affect the health of children with Prader-Willi syndrome (PWS). The gene among the genes in the Prader-Willi syndrome deletion region is expressed in proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC). Knockout of the gene disrupts POMC neuronal circuits and functions. Here, we report that loss of the gene exclusively in ARC neurons innervating the medial amygdala (MeA) causes a reduction in body weight in both male and female mice fed with a high-fat diet. This anti-obesity effect is associated with an increased locomotor activity. There are no significant differences in glucose and insulin tolerance in mice without the gene in ARC neurons innervating the MeA. Plasma estrogen levels are higher in female mutant mice than in controls. Blockade of the G protein-coupled estrogen receptor (GPER), but not estrogen receptor-α (ER-α), reduces locomotor activity in female mutant mice. Hence, our study provides evidence that knockdown of the gene in ARC neurons innervating the MeA reduces susceptibility to diet-induced obesity with increased locomotor activity through activation of central GPER.
贪食症和肥胖症严重影响了 Prader-Willi 综合征（PWS）患儿的健康。PWS 缺失区域的基因在弓状核的 proopiomelanocortin（POMC）神经元中表达。该基因的敲除破坏了 POMC 神经元回路和功能。在这里，我们报告说，仅在支配内侧杏仁核（MeA）的 ARC 神经元中缺失该基因会导致雄性和雌性高脂饮食喂养的小鼠体重减轻。这种抗肥胖作用与运动活性增加有关。在不影响 ARC 神经元支配 MeA 的情况下，小鼠的葡萄糖和胰岛素耐量没有显著差异。雌性突变小鼠的血浆雌激素水平高于对照。阻断 G 蛋白偶联雌激素受体（GPER），而不是雌激素受体-α（ER-α），可降低雌性突变小鼠的运动活性。因此，我们的研究提供了证据，证明敲低 ARC 神经元支配 MeA 的 基因可通过激活中枢 GPER 增加运动活性，降低对饮食诱导肥胖的易感性。
