title: Prohibitin overexpression in adipocytes induces mitochondrial biogenesis, leads to obesity development, and affects glucose homeostasis in a sex-specific manner.
abstract: Adipocytes are the primary cells in the body that store excess energy 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. We developed a transgenic mouse model, Mito-Ob, overexpressing prohibitin (PHB) in adipocytes. Mito-Ob mice developed obesity due to upregulation of mitochondrial biogenesis in adipocytes. Of note, Mito-Ob female mice developed more visceral fat than male mice. 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. Mechanistically, we found that PHB overexpression enhances the cross talk between the mitochondria and the nucleus and facilitates mitochondrial biogenesis. 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. Targeting adipocyte mitochondria may provide new therapeutic opportunities for the treatment of obesity, a major risk factor for type 2 diabetes.
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Sudharsana R
authors.initials: SR
authors.lastname: Ande
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: K Hoa
authors.initials: KH
authors.lastname: Nguyen
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: G Pauline
authors.initials: GP
authors.lastname: Padilla-Meier
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Wahida
authors.initials: W
authors.lastname: Wahida
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: B L Grégoire
authors.initials: BL
authors.lastname: Nyomba
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada suresh.mishra@med.umanitoba.ca.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mishra
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D063269:Mitochondrial Turnover / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D000091402:Prohibitins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors
chemical_list: D052242:Adiponectin; D007328:Insulin; D000091402:Prohibitins; D012097:Repressor Proteins; D005947:Glucose