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

Jibran A. Wali, Sandra Galic, Christina YR Tan, Esteban N Gurzov, Ann E Frazier, Timothy Connor, Jingjing Ge, Evan G Pappas, David Stroud, L Chitra Varanasi, Claudia Selck, Michael T Ryan, David R. Thorburn, Bruce E Kemp, Balasubramanian Krishnamurthy, Thomas WH Kay, Sean L McGee, Helen E Thomas

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)217-225
Number of pages9
JournalCell Death and Differentiation
Volume25
Issue number1
DOIs
Publication statusPublished - 20 Oct 2017

Keywords

  • endocrine system and metabolic diseases
  • experimental models of disease

Cite this