Prohibitin overexpression in adipocyte induces mitochondrial biogenesis, leads to obesity development and affects whole‐body metabolism in a gender specific manner (765.3)

Abstract

Objective: Adipocyte is the primary cell in the body where excess energy is stored as triglycerides. 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.Results: We developed a transgenic mouse model, namely “Mito‐Ob”, overexpressing prohibitin in adipocytes. Mito‐Ob mice developed obesity due to upregulation of mitochondrial biogenesis in adipocytes. Interestingly, Mito‐Ob female mice developed more visceral fat than Mito‐Ob male mice. However, female mic preserved insulin sensitivity and had high adiponectin levels, whereas male mice became insulin resistant, had compromised brown adipose tissue structure and function and low adiponectin levels. Mechanistically, we found that prohibitin overexpression enhances the crosstalk between mitochondria and nucleus and facilitates mitochondrial biogenesis.Conclusions: Our data suggests a critical role of prohibitin and adipocyte mitochondria in adipose tissue homeostasis and reveals gender differences on the effect of adipocyte mitochondrial remodeling on whole‐body metabolism. Targeting adipocyte mitochondria may provide new therapeutic opportunities for obesity treatment.