PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis.

PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis.
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DOI:
10.1016/j.cmet.2010.05.002
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发表时间:
2010-07-07
期刊:
影响因子:
29
通讯作者:
Elmquist JK
Elmquist JK
中科院分区:
生物学1区
文献类型:
--
作者:
Xu Y;Hill JW;Fukuda M;Gautron L;Sohn JW;Kim KW;Lee CE;Choi MJ;Lauzon DA;Dhillon H;Lowell BB;Zigman JM;Zhao JJ;Elmquist JK

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下丘脑中的磷脂酰肌醇3-激酶(PI 3 K)信号转导与能量稳态的调节有关,但这种细胞内信号整合各种代谢线索以调节食物摄入和能量消耗的关键大脑部位尚不清楚。在这里,我们表明,在下丘脑腹内侧核(VMH)的PI 3 K活性降低的小鼠更敏感的高脂肪饮食诱导的肥胖,由于减少能量消耗。此外,VMH中PI 3 K的抑制损害了响应于急性高脂饮食喂养和食物剥夺而改变能量消耗的能力。此外,外源性瘦素诱导的急性肥胖效应在突变小鼠中减弱。总的来说,我们的研究结果表明,在VMH神经元中的PI 3 K活性在能量消耗的调节中起着生理相关的作用。
Phosphatidyl inositol 3-kinase (PI3K) signalling in the hypothalamus has been implicated in the regulation of energy homeostasis, but the critical brain sites where this intracellular signal integrates various metabolic cues to regulate food intake and energy expenditure are unknown. Here we show that mice with reduced PI3K activity in the ventromedial hypothalamic nucleus (VMH) are more sensitive to high fat diet-induced obesity due to reduced energy expenditure. In addition, inhibition of PI3K in the VMH impaired the ability to alter energy expenditure in response to acute high fat diet feeding and food deprivation. Furthermore, the acute anorexigenic effects induced by exogenous leptin were blunted in the mutant mice. Collectively, our results indicate that PI3K activity in VMH neurons plays a physiologically relevant role in the regulation of energy expenditure.
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