Journal article

JNK activation of BIM promotes hepatic oxidative stress, steatosis, and insulin resistance in obesity

SA Litwak, L Pang, S Galic, M Igoillo-Esteve, WJ Stanley, JV Turatsinze, K Loh, HE Thomas, A Sharma, E Trepo, C Moreno, DJ Gough, DL Eizirik, JB De Haan, EN Gurzov

Diabetes | AMER DIABETES ASSOC | Published : 2017

Abstract

The members of the BCL-2 family are crucial regulators of the mitochondrial pathway of apoptosis in normal physiology and disease. Besides their role in cell death, BCL-2 proteins have been implicated in the regulation of mitochondrial oxidative phosphorylation and cellular metabolism. It remains unclear, however, whether these proteins have a physiological role in glucose homeostasis and metabolism in vivo. In this study, we report that fat accumulation in the liver increases c-Jun N-terminal kinase-dependent BCL-2 interacting mediator of cell death (BIM) expression in hepatocytes. To determine the consequences of hepatic BIM deficiency in diet-induced obesity, we generated liverspecific BI..

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University of Melbourne Researchers

Grants

Awarded by Juvenile Diabetes Research Foundation United States of America


Funding Acknowledgements

This work was supported by a National Health and Medical Research Council of Australia project grant (APP1071350). E.N.G. is supported by a JDRF fellowship. St. Vincent's Institute receives support from the Operational Infrastructure Support Scheme of the Government of Victoria.