Polak Pazit, Cybulski Nadine, Feige Jerome N, Auwerx Johan, Rüegg Markus A, Hall Michael N
Biozentrum, University of Basel, Basel, CH-4056, Switzerland.
Cell Metab. 2008 Nov;8(5):399-410. doi: 10.1016/j.cmet.2008.09.003.
raptor is a specific and essential component of mammalian TOR complex 1 (mTORC1), a key regulator of cell growth and metabolism. To investigate a role of adipose mTORC1 in regulation of adipose and whole-body metabolism, we generated mice with an adipose-specific knockout of raptor (raptor(ad-/-)). Compared to control littermates, raptor(ad-/-) mice had substantially less adipose tissue, were protected against diet-induced obesity and hypercholesterolemia, and exhibited improved insulin sensitivity. Leanness was in spite of reduced physical activity and unaffected caloric intake, lipolysis, and absorption of lipids from the food. White adipose tissue of raptor(ad-/-) mice displayed enhanced expression of genes encoding mitochondrial uncoupling proteins characteristic of brown fat. Leanness of the raptor(ad-/-) mice was attributed to elevated energy expenditure due to mitochondrial uncoupling. These results suggest that adipose mTORC1 is a regulator of adipose metabolism and, thereby, controls whole-body energy homeostasis.
Raptor是哺乳动物雷帕霉素靶蛋白复合物1（mTORC1）的一个特定且必需的组成部分，mTORC1是细胞生长和代谢的关键调节因子。为了研究脂肪组织中的mTORC1在脂肪和全身代谢调节中的作用，我们构建了具有脂肪特异性敲除Raptor的小鼠（raptor(ad-/-)）。与对照同窝小鼠相比，raptor(ad-/-)小鼠的脂肪组织显著减少，对饮食诱导的肥胖和高胆固醇血症具有抵抗力，并且表现出改善的胰岛素敏感性。尽管身体活动减少且热量摄入、脂肪分解以及食物中脂质的吸收未受影响，但它们仍保持消瘦。raptor(ad-/-)小鼠的白色脂肪组织中，编码棕色脂肪特有的线粒体解偶联蛋白的基因表达增强。raptor(ad-/-)小鼠的消瘦归因于线粒体解偶联导致的能量消耗增加。这些结果表明，脂肪组织中的mTORC1是脂肪代谢的调节因子，从而控制全身能量稳态。
