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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.

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


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.

[Available on 2019-01-01]
[Indexed for MEDLINE]

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