Zhang Chongben, Yoon Mee-Sup, Chen Jie
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E862-8. doi: 10.1152/ajpendo.90651.2008. Epub 2009 Feb 3.
Chronically high insulin levels and increased circulating free fatty acids released from adipose tissue through lipolysis are two features associated with insulin resistance. The relationship between chronic insulin exposure and adipocyte lipolysis has been unclear. In the present study we found that chronic insulin exposure in 3T3-L1 adipocytes, as well as in mouse primary adipocytes, increased basal lipolysis rates. This effect of insulin on lipolysis was only observed when the mammalian target of rapamycin (mTOR) pathway was inhibited by rapamycin in the adipocytes. In addition, amino acid deprivation in adipocytes phenocopied the effect of rapamycin in permitting the stimulation of lipolysis by chronic insulin exposure. The phosphatidylinositol 3-kinase-Akt pathway does not appear to be involved in this insulin effect. Furthermore, we found that triacylglycerol hydrolase (TGH) activity was required for the stimulation of lipolysis by combined exposure to insulin and rapamycin. Therefore, we propose that nutrient sufficiency, mediated by an mTOR pathway, suppresses TGH-dependent lipolysis stimulated by chronic insulin exposure in adipocytes.
长期高水平的胰岛素以及通过脂解作用从脂肪组织释放的循环游离脂肪酸增加是与胰岛素抵抗相关的两个特征。慢性胰岛素暴露与脂肪细胞脂解之间的关系尚不清楚。在本研究中，我们发现3T3-L1脂肪细胞以及小鼠原代脂肪细胞中的慢性胰岛素暴露会增加基础脂解速率。只有当雷帕霉素在脂肪细胞中抑制哺乳动物雷帕霉素靶蛋白（mTOR）途径时，才会观察到胰岛素对脂解的这种作用。此外，脂肪细胞中的氨基酸剥夺模拟了雷帕霉素在允许慢性胰岛素暴露刺激脂解方面的作用。磷脂酰肌醇3-激酶-Akt途径似乎不参与这种胰岛素作用。此外，我们发现联合暴露于胰岛素和雷帕霉素刺激脂解需要三酰甘油水解酶（TGH）活性。因此，我们提出由mTOR途径介导的营养充足会抑制脂肪细胞中慢性胰岛素暴露刺激的TGH依赖性脂解。
