Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects From Diet-Induced Obesity

Cell Rep. 2016 Feb 23;14(7):1602-1610. doi: 10.1016/j.celrep.2016.01.046. Epub 2016 Feb 11.

Abstract

Mitochondrial carrier homolog 2 (MTCH2) is a repressor of mitochondrial oxidative phosphorylation (OXPHOS), and its locus is associated with increased BMI in humans. Here, we demonstrate that mice deficient in muscle MTCH2 are protected from diet-induced obesity and hyperinsulinemia and that they demonstrate increased energy expenditure. Deletion of muscle MTCH2 also increases mitochondrial OXPHOS and mass, triggers conversion from glycolytic to oxidative fibers, increases capacity for endurance exercise, and increases heart function. Moreover, metabolic profiling of mice deficient in muscle MTCH2 reveals a preference for carbohydrate utilization and an increase in mitochondria and glycolytic flux in muscles. Thus, MTCH2 is a critical player in muscle biology, modulating metabolism and mitochondria mass as well as impacting whole-body energy homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Composition
  • Diet, High-Fat
  • Disease Models, Animal
  • Energy Metabolism
  • Gene Expression
  • Glycolysis / genetics
  • Humans
  • Male
  • Metabolome / genetics*
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Membrane Transport Proteins / deficiency
  • Mitochondrial Membrane Transport Proteins / genetics*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Obesity / etiology
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Oxidative Phosphorylation
  • Physical Conditioning, Animal

Substances

  • Mitochondrial Membrane Transport Proteins
  • Mtch2 protein, mouse