Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Comprehensive Center on Obesity, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Obesity (Silver Spring). 2014 Jun;22(6):1477-84. doi: 10.1002/oby.20719. Epub 2014 Feb 19.
Androgen excess in women is associated with visceral adiposity. However, little is known on the mechanism through which androgen promotes visceral fat accumulation.
To address this issue, female mice to chronic androgen excess using 5α-dihydrotestosterone (DHT) and studied the regulation of energy homeostasis was exposed.
DHT induced a leptin failure to decrease body weight associated with visceral adiposity but without alterations in leptin anorectic action. This paralleled leptin's failure to upregulate brown adipose tissue expression of uncoupling protein-1, associated with decreased energy expenditure (EE). DHT decreased hypothalamic proopiomelanocortin (pomc) mRNA expression and increased POMC intensity in neuronal bodies of the arcuate nucleus while simultaneously decreasing the intensity of POMC projections to the dorsomedial hypothalamus (DMH). This was associated with a failure of the melanocortin 4 receptor agonist melanotan-II to suppress body weight.
Taken together, these data indicate that androgen excess promotes visceral adiposity with reduced POMC neuronal innervation in the DMH, reduced EE but without hyperphagia.
女性雄激素过多与内脏脂肪堆积有关。然而，雄激素促进内脏脂肪堆积的机制知之甚少。
为了解决这个问题，雌性小鼠通过 5α-二氢睾酮（DHT）暴露于慢性雄激素过多，并研究了能量平衡的调节。
DHT 诱导瘦素失效，导致体重增加与内脏肥胖有关，但不会改变瘦素的厌食作用。这与瘦素不能上调解偶联蛋白-1在棕色脂肪组织中的表达相一致，与能量消耗（EE）减少有关。DHT 降低了下丘脑前阿黑皮素原（pomc）mRNA 的表达，并增加了弓状核神经元体中 POMC 的强度，同时减少了 POMC 投射到下丘脑背内侧核（DMH）的强度。这与促黑素细胞皮质素 4 受体激动剂黑素瘤 II 不能抑制体重的作用有关。
综上所述，这些数据表明，雄激素过多会导致内脏脂肪堆积，同时 DMH 中 POMC 神经元传入减少，能量消耗减少，但摄食量没有增加。
