Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice

Cell Death Differ. 2018 Jan;25(1):217-225. doi: 10.1038/cdd.2017.168. Epub 2017 Oct 20.

Abstract

BCL-2 proteins are known to engage each other to determine the fate of a cell after a death stimulus. However, their evolutionary conservation and the many other reported binding partners suggest an additional function not directly linked to apoptosis regulation. To identify such a function, we studied mice lacking the BH3-only protein BIM. BIM-/- cells had a higher mitochondrial oxygen consumption rate that was associated with higher mitochondrial complex IV activity. The consequences of increased oxygen consumption in BIM-/- mice were significantly lower body weights, reduced adiposity and lower hepatic lipid content. Consistent with reduced adiposity, BIM-/- mice had lower fasting blood glucose, improved insulin sensitivity and hepatic insulin signalling. Lipid oxidation was increased in BIM-/- mice, suggesting a mechanism for their metabolic phenotype. Our data suggest a role for BIM in regulating mitochondrial bioenergetics and metabolism and support the idea that regulation of metabolism and cell death are connected.

MeSH terms

  • Adiposity*
  • Animals
  • Bcl-2-Like Protein 11 / genetics
  • Bcl-2-Like Protein 11 / physiology*
  • Electron Transport Complex IV / metabolism
  • Energy Metabolism
  • Glucose / metabolism
  • Hepatocytes / metabolism
  • Insulin Resistance
  • Lipid Metabolism*
  • Liver / metabolism
  • Membrane Potential, Mitochondrial
  • Mice
  • Mitochondria / metabolism*
  • Oxidation-Reduction
  • Oxygen Consumption
  • Weight Loss

Substances

  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Electron Transport Complex IV
  • Glucose