• Citer

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

par Wali, Jibran A;Galic, Sandra;Tan, Christina Yr;Gurzov, Esteban Nicolas ;Frazier, Ann AE;Connor, Timothy;Ge, Jingjing;Pappas, Evan G;Stroud, David;Varanasi, Chitra LC;Selck, Claudia;Ryan, Michael T;Thorburn, David DR;Kemp, Bruce E;Krishnamurthy, Balasubramanian;Kay, Thomas Wh;McGee, Sean SL;Thomas, Helen H.E.
Référence Cell death and differentiation
Publication Publié, 2017-10

Article révisé par les pairs

• Détails
• Contenu

Résumé :

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.Cell Death and Differentiation advance online publication, 20 October 2017; doi:10.1038/cdd.2017.168.