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

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

Author information

1
St. Vincent's Institute, Fitzroy, VIC 3065, Australia.
2
The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, VIC 3065, Australia.
3
Murdoch Childrens Research Institute and The University of Melbourne Department of Paediatrics, Royal Childrens Hospital, Parkville, VIC 3052, Australia.
4
Metabolic Reprogramming Laboratory, Metabolic Research Unit, School of Medicine, Deakin University, Geelong, VIC 3216, Australia.
5
Department of Biochemistry and Molecular Biology, Monash University, VIC 3800, Australia.
6
Victorian Clinical Genetics Services, Royal Childrens Hospital, Parkville, VIC 3052, Australia.

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.

PMID:
29053141
PMCID:
PMC5729528
[Available on 2019-01-01]
DOI:
10.1038/cdd.2017.168
[Indexed for MEDLINE]

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