University of Queensland Centre for Clinical Research, Faculty of Medicine, Brisbane, Qld, Australia.
Department of Neurology, Royal Brisbane & Women's Hospital, Brisbane, Qld, Australia.
Aging Cell. 2018 Feb;17(1). doi: 10.1111/acel.12703. Epub 2017 Nov 23.
Weight loss is an effective intervention for diminishing disease burden in obese older adults. Pharmacological interventions that reduce food intake and thereby promote weight loss may offer effective strategies to reduce age-related disease. We previously reported that 17α-estradiol (17α-E2) administration elicits beneficial effects on metabolism and inflammation in old male mice. These observations were associated with reduced calorie intake. Here, we demonstrate that 17α-E2 acts through pro-opiomelanocortin (Pomc) expression in the arcuate nucleus (ARC) to reduce food intake and body mass in mouse models of obesity. These results confirm that 17α-E2 modulates appetite through selective interactions within hypothalamic anorexigenic pathways. Interestingly, some peripheral markers of metabolic homeostasis were also improved in animals with near complete loss of ARC Pomc transcription. This suggests that 17α-E2 might have central and peripheral actions that can beneficially affect metabolism cooperatively or independently.
体重减轻是减少肥胖老年患者疾病负担的有效干预措施。减少食物摄入从而促进体重减轻的药物干预可能提供减少与年龄相关疾病的有效策略。我们之前报道过，17α-雌二醇（17α-E2）的给药对老年雄性小鼠的代谢和炎症产生有益影响。这些观察结果与减少热量摄入有关。在这里，我们证明 17α-E2 通过在弓状核（ARC）中表达 pro-opiomelanocortin（Pomc）来减少肥胖小鼠模型的食物摄入和体重。这些结果证实，17α-E2 通过选择性地作用于下丘脑食欲抑制途径来调节食欲。有趣的是，ARC Pomc 转录几乎完全缺失的动物的一些代谢稳态的外周标志物也得到了改善。这表明，17α-E2 可能具有中枢和外周作用，可以协同或独立地有益于代谢。
