Shi Haifei, Strader April D, Sorrell Joyce E, Chambers James B, Woods Stephen C, Seeley Randy J
Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45237, USA.
Am J Physiol Endocrinol Metab. 2008 Mar;294(3):E630-9. doi: 10.1152/ajpendo.00704.2007. Epub 2008 Jan 2.
Leptin regulates energy balance and glucose homeostasis, at least in part, via activation of receptors in the arcuate nucleus of the hypothalamus located in proopiomelanocortin (POMC) neurons. Females have greater sensitivity to central leptin than males, suggested by a greater anorectic effect of central leptin administration in females. We hypothesized that the regulation of energy balance and peripheral glucose homeostasis of female rodents would be affected to a greater extent than in males if the action of leptin in POMC neurons were disturbed. Male and female mice lacking leptin receptors only in POMC neurons gained significantly more body weight and accumulated more body fat. However, female mice gained disproportionately more visceral adiposity than males, and this appeared to be largely the result of differences in energy expenditure. When maintained on a high-fat diet (HFD), both male and female mutants had higher levels of insulin following exogenous glucose challenges. Chow- and HFD-fed males but not females had abnormal glucose disappearance curves following insulin administrations. Collectively, these data indicate that the action of leptin in POMC neurons is sexually different to influence the regulation of energy balance, fat distribution, and glucose homeostasis.
瘦素至少部分地通过激活位于促黑素细胞皮质激素（POMC）神经元中的下丘脑弓状核受体来调节能量平衡和葡萄糖稳态。雌性对中枢瘦素的敏感性高于雄性，这一点由中枢给予瘦素时雌性更强的厌食效应所表明。我们推测，如果POMC神经元中瘦素的作用受到干扰，雌性啮齿动物的能量平衡和外周葡萄糖稳态的调节将比雄性受到更大程度的影响。仅在POMC神经元中缺乏瘦素受体的雄性和雌性小鼠体重显著增加，体脂积累更多。然而，雌性小鼠比雄性小鼠内脏脂肪增加得更多，这似乎主要是能量消耗差异的结果。当维持高脂饮食（HFD）时，雄性和雌性突变体在给予外源性葡萄糖刺激后胰岛素水平都较高。喂食普通饲料和HFD的雄性小鼠而非雌性小鼠在注射胰岛素后葡萄糖消失曲线异常。总体而言，这些数据表明，POMC神经元中瘦素的作用在性别上存在差异，从而影响能量平衡、脂肪分布和葡萄糖稳态的调节。
