Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Cell Rep. 2019 Mar 12;26(11):2849-2858.e4. doi: 10.1016/j.celrep.2019.02.039.
We found that exposure of adult animals to calorie-dense foods rapidly abolished expression of mitofusin 2 (Mfn2), a gene promoting mitochondrial fusion and mitochondrion-endoplasmic reticulum interactions, in white and brown fat. Mfn2 mRN was also robustly lower in obese human subjects compared with lean controls. Adipocyte-specific knockdown of Mfn2 in adult mice led to increased food intake, adiposity, and impaired glucose metabolism on standard chow as well as on a diet with high calorie content. The body weight and adiposity of mature adipocyte-specific Mfn2 knockout mice on a standard diet were similar to those of control mice on a high-fat diet. The transcriptional profile of the adipose tissue in adipocyte-specific Mfn2 knockout mice was consistent with adipocyte proliferation, increased lipogenesis at the tissue level, and decreased glucose utilization at the systemic level. These observations suggest a possible crucial role for mitochondrial dynamics in adipocytes in initiating systemic metabolic dysregulation.
我们发现，成年动物暴露于高热量食物中会迅速导致白色和棕色脂肪中线粒体融合和线粒体-内质网相互作用的促进基因——线粒体融合蛋白 2（Mfn2）的表达被消除。与瘦对照组相比，肥胖的人类受试者中 Mfn2mRNA 的表达也明显降低。成年小鼠脂肪细胞特异性敲低 Mfn2 会导致食物摄入量增加、肥胖和葡萄糖代谢受损，无论是在标准饲料还是高热量含量的饮食中。在标准饮食下，成熟脂肪细胞特异性 Mfn2 敲除小鼠的体重和肥胖程度与高脂肪饮食下的对照组小鼠相似。脂肪细胞特异性 Mfn2 敲除小鼠脂肪组织的转录谱与脂肪细胞增殖一致，组织水平的脂肪生成增加，全身水平的葡萄糖利用减少。这些观察结果表明，线粒体动力学在脂肪细胞中可能对引发全身代谢失调起着至关重要的作用。
