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瘦素受体在 POMC 神经元中对性别特异性能量平衡调节的作用。

The roles of leptin receptors on POMC neurons in the regulation of sex-specific energy homeostasis.

机构信息

Department of Zoology, Miami University, Oxford, OH, United States.

出版信息

Physiol Behav. 2010 May 11;100(2):165-72. doi: 10.1016/j.physbeh.2010.02.018. Epub 2010 Mar 1.

DOI:10.1016/j.physbeh.2010.02.018
PMID:20193700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3608195/
Abstract

Leptin regulates energy homeostasis and reproduction. One key population of leptin receptors (Lepr) are found on proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus, and evidence links the action of gonadal estrogens to these same POMC neurons. To determine whether Lepr on POMC neurons are critical for reproductive capacity or for sex-specific energy and glucose homeostasis, we studied Cre/loxP mice lacking Lepr specifically on POMC neurons (Pomc-Cre, Lepr(flox/flox) mice) and their controls with normal Lepr (Lepr(flox/flox) mice). Pomc-Cre, Lepr(flox/flox) mice maintained normal reproductive capacity and accumulated more body fat than their same sex controls. Ovariectomy (OVX) was performed to investigate the effects of the estrogens and Lepr on POMC neurons on body fat accumulation and glucose tolerance. OVX Pomc-Cre, Lepr(flox/flox) females accumulated more fat than OVX Lepr(flox/flox) females did. Pomc-Cre, Lepr(flox/flox) males were glucose intolerant and insulin insensitive compared with control males. In contrast, control and Pomc-Cre, Lepr(flox/flox) females had similar glucose tolerance before and after OVX. Therefore leptin's action on POMC neurons reduces body fat accumulation, but is not critical for regulation of reproduction. The sex difference in leptin signaling on POMC neurons on glucose tolerance appears independent of ovarian hormones.

摘要

瘦素调节能量平衡和生殖。瘦素受体（Lepr）的一个关键群体存在于下丘脑弓状核的 proopiomelanocortin（POMC）神经元上，有证据表明，性腺雌激素的作用与这些相同的 POMC 神经元有关。为了确定 POMC 神经元上的 Lepr 是否对生殖能力或性别特异性能量和葡萄糖平衡至关重要，我们研究了专门在 POMC 神经元上缺乏 Lepr 的 Cre/loxP 小鼠（Pomc-Cre，Lepr(flox/flox) 小鼠）及其具有正常 Lepr 的对照（Lepr(flox/flox) 小鼠）。Pomc-Cre，Lepr(flox/flox) 小鼠保持正常的生殖能力，并比其相同性别的对照积累更多的体脂肪。进行卵巢切除术（OVX）以研究雌激素和 Lepr 对 POMC 神经元对体脂肪积累和葡萄糖耐量的影响。OVX Pomc-Cre，Lepr(flox/flox) 雌性比 OVX Lepr(flox/flox) 雌性积累更多的脂肪。与对照雄性相比，Pomc-Cre，Lepr(flox/flox) 雄性不耐受葡萄糖且胰岛素不敏感。相比之下，在 OVX 前后，对照和 Pomc-Cre，Lepr(flox/flox) 雌性的葡萄糖耐量相似。因此，瘦素对 POMC 神经元的作用可减少体脂肪积累，但对生殖调节并非至关重要。POMC 神经元上瘦素信号对葡萄糖耐量的性别差异似乎与卵巢激素无关。

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