![]() ![]() A: The top panels show body weight of the Mito-Ob mice and their Wt littermates from three different transgenic lines at 3 months of age ( n = 8–10 mice/group). ![]() Growth curve and adipose tissue weight in the Mito-Ob mice. Targeting adipocyte mitochondria may provide new therapeutic opportunities for the treatment of obesity, a major risk factor for type 2 diabetes. The data suggest a critical role of PHB and adipocyte mitochondria in adipose tissue homeostasis and reveal sex differences in the effect of PHB-induced adipocyte mitochondrial remodeling on whole-body metabolism. Mechanistically, we found that PHB overexpression enhances the cross talk between the mitochondria and the nucleus and facilitates mitochondrial biogenesis. However, female mice exhibited no change in glucose homeostasis and had normal insulin and high adiponectin levels, whereas male mice had impaired glucose homeostasis, compromised brown adipose tissue structure, and high insulin and low adiponectin levels. Of note, Mito-Ob female mice developed more visceral fat than male mice. Mito-Ob mice developed obesity due to upregulation of mitochondrial biogenesis in adipocytes. We developed a transgenic mouse model, Mito-Ob, overexpressing prohibitin (PHB) in adipocytes. To perform this specialized function, adipocytes rely on their mitochondria however, the role of adipocyte mitochondria in the regulation of adipose tissue homeostasis and its impact on metabolic regulation is not understood. Adipocytes are the primary cells in the body that store excess energy as triglycerides.
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