STAT5 ablation in AgRP neurons increases female adiposity and blunts food restriction adaptations
STAT5 ablation in AgRP neurons increases female adiposity and blunts food restriction adaptations
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DOI：
10.1530/jme-19-0158
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发表时间：
2020-01-01
影响因子：
3.5
通讯作者：
Donato Jr, Jose
中科院分区：
文献类型：
--
作者：
Furigo, Isadora C.;Teixeira, Pryscila D. S.;Donato Jr, Jose
AgRP神经元是控制能量动态平衡的重要角色，对几种激素有反应。此外，大脑中的STAT5信号由代谢激素和生长因子激活，调节食物摄入量、体内脂肪和葡萄糖的动态平衡。鉴于这一点，以及缺乏关于STAT5在AgRP细胞中的功能的研究，本研究探讨了Stat5a/b基因去除对这些神经元的代谢影响。我们观察到AgRP神经元中的STAT5信号调节雌性小鼠的体脂。然而，与对照小鼠相比，雄性和雌性STAT5基因敲除小鼠没有表现出食物摄入、能量消耗或葡萄糖稳态的变化。AgRP特异性的STAT5消融也不影响2-脱氧-D-葡萄糖治疗引起的逆调节反应或葡萄糖过度吞噬。然而，在60%的食物限制下，AgRP STAT5基因敲除小鼠的下丘脑AgRP mRNA表达和皮质酮水平比对照小鼠迟钝地上调，这表明AgRP神经元中的STAT5可能在神经内分泌对食物限制的适应中发挥作用。有趣的是，与对照组相比，随意喂养的基因敲除雄性小鼠降低了POMC和UCP-1mRNA的表达。综上所述，这些结果表明，AgRP神经元中的STAT5信号调节雌性小鼠的身体肥胖，以及一些神经内分泌对食物限制的适应。
AgRP neurons are important players in the control of energy homeostasis and are responsive to several hormones. In addition, STAT5 signalling in the brain, which is activated by metabolic hormones and growth factors, modulates food intake, body fat and glucose homeostasis. Given that, and the absence of studies that describe STAT5 function in AgRP cells, the present study investigated the metabolic effects of Stat5a/b gene ablation in these neurons. We observed that STAT5 signalling in AgRP neurons regulates body fat in female mice. However, male and female STAT5-knockout mice did not exhibit altered food intake, energy expenditure or glucose homeostasis compared to control mice. The counter-regulatory response or glucoprivic hyperphagia induced by 2-deoxy-D-glucose treatment were also not affected by AgRP-specific STAT5 ablation. However, under 60% food restriction, AgRP STAT5-knockout mice had a blunted upregulation of hypothalamic Agrp mRNA expression and corticosterone serum levels compared to control mice, suggesting a possible role for STAT5 in AgRP neurons for neuroendocrine adaptations to food restriction. Interestingly, ad libitum fed knockout male mice had reduced Pomc and Ucp-1 mRNA expression compared to control group. Taken together, these results suggest that STAT5 signalling in AgRP neurons regulates body adiposity in female mice, as well as some neuroendocrine adaptations to food restriction.