mTORC2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue.
mTORC2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue.
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DOI：
10.15252/emmm.201505610
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发表时间：
2016-03-01
影响因子：
11.1
通讯作者：
Hall MN
中科院分区：
文献类型：
--
作者：
Albert V;Svensson K;Shimobayashi M;Colombi M;Muñoz S;Jimenez V;Handschin C;Bosch F;Hall MN
棕色脂肪组织（BAT）中非颤抖性产热（NST）的激活已被提议作为抗肥胖治疗。此外，冷诱导的葡萄糖摄取可以使胰岛素抵抗患者的血糖水平正常化。因此，重要的是要确定新的NST和冷诱导的葡萄糖摄取的调节剂。哺乳动物雷帕霉素复合物靶蛋白2（mTORC 2）介导代谢组织中胰岛素刺激的葡萄糖摄取，但其在NST中的作用尚不清楚。我们表明，mTORC 2在β-肾上腺素能刺激后在棕色脂肪细胞中被激活。此外，在脂肪组织中特异性缺乏mTORC 2的小鼠（AdRiKO小鼠）体温过低，表现出对冷的敏感性增加，并表现出冷诱导的葡萄糖摄取和糖酵解受损。通过过表达己糖激酶II或激活的Akt 2恢复BAT中的葡萄糖摄取足以增加AdRiKO小鼠的体温并改善其耐冷性。因此，BAT中的mTORC 2通过调节冷诱导的葡萄糖摄取来介导温度稳态。我们的研究结果证明了葡萄糖代谢在体温调节中的重要性。
Activation of non‐shivering thermogenesis (NST) in brown adipose tissue (BAT) has been proposed as an anti‐obesity treatment. Moreover, cold‐induced glucose uptake could normalize blood glucose levels in insulin‐resistant patients. It is therefore important to identify novel regulators of NST and cold‐induced glucose uptake. Mammalian target of rapamycin complex 2 (mTORC2) mediates insulin‐stimulated glucose uptake in metabolic tissues, but its role in NST is unknown. We show that mTORC2 is activated in brown adipocytes upon β‐adrenergic stimulation. Furthermore, mice lacking mTORC2 specifically in adipose tissue (AdRiKO mice) are hypothermic, display increased sensitivity to cold, and show impaired cold‐induced glucose uptake and glycolysis. Restoration of glucose uptake in BAT by overexpression of hexokinase II or activated Akt2 was sufficient to increase body temperature and improve cold tolerance in AdRiKO mice. Thus, mTORC2 in BAT mediates temperature homeostasis via regulation of cold‐induced glucose uptake. Our findings demonstrate the importance of glucose metabolism in temperature regulation.