Mitofusin 2 in Mature Adipocytes Controls Adiposity and Body Weight

Cell Rep. 2019 Mar 12;26(11):2849-2858.e4. doi: 10.1016/j.celrep.2019.02.039.

Abstract

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.

Keywords: mitochondria; mitofusin; obesity; white adipocyte.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Adipocytes / physiology
  • Adiposity*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Body Weight*
  • Cell Proliferation
  • Eating
  • Female
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Glucose / metabolism
  • Humans
  • Lipogenesis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Mitochondrial Dynamics
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Transcriptome

Substances

  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • MFN2 protein, human
  • Mfn2 protein, mouse
  • Glucose