Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice.
Jibran A WaliSandra GalicChristina Yr TanEsteban Nicolas GurzovAnn E FrazierTimothy ConnorJingjing GeEvan G PappasDavid StroudL Chitra VaranasiClaudia SelckMichael T RyanDavid R ThorburnBruce E KempBalasubramanian KrishnamurthyThomas Wh KaySean L McGeeHelen E ThomasPublished in: Cell death and differentiation (2017)
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.
Keyphrases
- high fat diet induced
- blood glucose
- oxidative stress
- cell death
- insulin resistance
- cell cycle arrest
- type diabetes
- induced apoptosis
- stem cells
- fatty acid
- adipose tissue
- hydrogen peroxide
- glycemic control
- single cell
- dna methylation
- weight gain
- blood pressure
- cell proliferation
- gene expression
- genome wide
- protein protein
- men who have sex with men