Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Exp Mol Med. 2019 Apr 26;51(4):1-9. doi: 10.1038/s12276-019-0249-8.
Phosphoinositide 3-kinase (PI3K) signaling in hypothalamic neurons integrates peripheral metabolic cues, including leptin and insulin, to coordinate systemic glucose and energy homeostasis. PI3K is composed of different subunits, each of which has several unique isoforms. However, the role of the PI3K subunits and isoforms in the ventromedial hypothalamus (VMH), a prominent site for the regulation of glucose and energy homeostasis, is unclear. Here we investigated the role of subunit p110β in steroidogenic factor-1 (SF-1) neurons of the VMH in the regulation of metabolism. Our data demonstrate that the deletion of p110β in SF-1 neurons disrupts glucose metabolism, rendering the mice insulin resistant. In addition, the deletion of p110β in SF-1 neurons leads to the whitening of brown adipose tissues and increased susceptibility to diet-induced obesity due to blunted energy expenditure. These results highlight a critical role for p110β in the regulation of glucose and energy homeostasis via VMH neurons.
磷酸肌醇 3-激酶 (PI3K) 信号在下丘脑神经元中整合外周代谢信号，包括瘦素和胰岛素，以协调全身葡萄糖和能量稳态。PI3K 由不同的亚基组成，每个亚基都有几个独特的同工型。然而，PI3K 亚基和同工型在腹内侧下丘脑 (VMH) 中的作用尚不清楚，VMH 是调节葡萄糖和能量稳态的重要部位。在这里，我们研究了亚基 p110β 在 VMH 中的类固醇生成因子-1 (SF-1) 神经元中对代谢的调节作用。我们的数据表明，SF-1 神经元中 p110β 的缺失会破坏葡萄糖代谢，使小鼠对胰岛素产生抗性。此外，SF-1 神经元中 p110β 的缺失会导致棕色脂肪组织变白，并由于能量消耗减弱而增加对饮食诱导肥胖的易感性。这些结果突出了 p110β 通过 VMH 神经元在调节葡萄糖和能量稳态中的关键作用。
