Mitofusin 2 in Mature Adipocytes Controls Adiposity and Body Weight

We found that exposure of adult animals to caloriedense foods rapidly abolished expression of mitofusin 2 (Mfn2), a gene promoting mitochondria! 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 mitochondria! dynamics in adipocytes in initiating systemic metabolic dysregulation.