Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02115, USA.
Cell Metab. 2012 Dec 5;16(6):765-76. doi: 10.1016/j.cmet.2012.10.016. Epub 2012 Nov 15.
Obesity and type 2 diabetes are associated with mitochondrial dysfunction in adipose tissue, but the role for adipose tissue mitochondria in the development of these disorders is currently unknown. To understand the impact of adipose tissue mitochondria on whole-body metabolism, we have generated a mouse model with disruption of the mitochondrial transcription factor A (TFAM) specifically in fat. F-TFKO adipose tissue exhibit decreased mtDNA copy number, altered levels of proteins of the electron transport chain, and perturbed mitochondrial function with decreased complex I activity and greater oxygen consumption and uncoupling. As a result, F-TFKO mice exhibit higher energy expenditure and are protected from age- and diet-induced obesity, insulin resistance, and hepatosteatosis, despite a greater food intake. Thus, TFAM deletion in the adipose tissue increases mitochondrial oxidation that has positive metabolic effects, suggesting that regulation of adipose tissue mitochondria may be a potential therapeutic target for the treatment of obesity.
肥胖症和 2 型糖尿病与脂肪组织中线粒体功能障碍有关，但脂肪组织线粒体在这些疾病发展中的作用目前尚不清楚。为了了解脂肪组织线粒体对全身代谢的影响，我们生成了一种脂肪组织中特异性敲除线粒体转录因子 A (TFAM)的小鼠模型。F-TFKO 脂肪组织的 mtDNA 拷贝数减少，电子传递链蛋白水平改变，线粒体功能受到干扰，复合物 I 活性降低，耗氧量和解偶联增加。结果，F-TFKO 小鼠表现出更高的能量消耗，并且能够预防年龄和饮食诱导的肥胖、胰岛素抵抗和肝脂肪变性，尽管它们的食物摄入量更多。因此，脂肪组织中 TFAM 的缺失增加了线粒体氧化，从而产生了积极的代谢效应，这表明调节脂肪组织线粒体可能是治疗肥胖症的一个潜在治疗靶点。
