JNK Activation of BIM Promotes Hepatic Oxidative Stress, Steatosis, and Insulin Resistance in Obesity
Sara A Litwak, Lokman Pang, Sandra Galic, Mariana Igoillo-Esteve, William J Stanley, Jean-Valery Turatsinze, Kim Loh, Helen E Thomas, Arpeeta Sharma, Eric Trepo, Christophe Moreno, Daniel J Gough, Decio L Eizirik, Judy B de Haan, Esteban N Gurzov
Diabetes | AMER DIABETES ASSOC | Published : 2017
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 liver-specific B..View full abstract
Awarded by National Health and Medical Research Council of Australia
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.