Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Diabetes. 2014 Nov;63(11):3734-41. doi: 10.2337/db13-1807. Epub 2014 Jun 19.
Adipocytes are the primary cells in the body that store excess energy as triglycerides. To perform this specialized function, adipocytes rely on their mitochondria; however, the role of adipocyte mitochondria in the regulation of adipose tissue homeostasis and its impact on metabolic regulation is not understood. We developed a transgenic mouse model, Mito-Ob, overexpressing prohibitin (PHB) in adipocytes. Mito-Ob mice developed obesity due to upregulation of mitochondrial biogenesis in adipocytes. Of note, Mito-Ob female mice developed more visceral fat than male mice. However, female mice exhibited no change in glucose homeostasis and had normal insulin and high adiponectin levels, whereas male mice had impaired glucose homeostasis, compromised brown adipose tissue structure, and high insulin and low adiponectin levels. Mechanistically, we found that PHB overexpression enhances the cross talk between the mitochondria and the nucleus and facilitates mitochondrial biogenesis. The data suggest a critical role of PHB and adipocyte mitochondria in adipose tissue homeostasis and reveal sex differences in the effect of PHB-induced adipocyte mitochondrial remodeling on whole-body metabolism. Targeting adipocyte mitochondria may provide new therapeutic opportunities for the treatment of obesity, a major risk factor for type 2 diabetes.
脂肪细胞是体内储存多余能量（三酰甘油）的主要细胞。为了执行这一特殊功能，脂肪细胞依赖于它们的线粒体；然而，脂肪细胞线粒体在调节脂肪组织稳态及其对代谢调节的影响方面的作用尚不清楚。我们开发了一种过表达 PHB 的脂肪细胞特异性转基因小鼠模型（Mito-Ob）。由于脂肪细胞中线粒体生物发生的上调，Mito-Ob 小鼠发生肥胖。值得注意的是，Mito-Ob 雌性小鼠比雄性小鼠更容易形成内脏脂肪。然而，雌性小鼠的葡萄糖稳态没有变化，胰岛素和脂联素水平正常，而雄性小鼠的葡萄糖稳态受损，棕色脂肪组织结构受损，胰岛素水平升高，脂联素水平降低。从机制上讲，我们发现 PHB 的过表达增强了线粒体和细胞核之间的串扰，并促进了线粒体生物发生。数据表明 PHB 和脂肪细胞线粒体在脂肪组织稳态中起着关键作用，并揭示了 PHB 诱导的脂肪细胞线粒体重塑对全身代谢的影响存在性别差异。靶向脂肪细胞线粒体可能为肥胖症的治疗提供新的治疗机会，肥胖症是 2 型糖尿病的主要危险因素。
