title: Reduced expression of mitochondrial frataxin in mice exacerbates diet-induced obesity.
abstract: Published evidence suggests that adiposity in humans may be linked to impaired energy expenditure for reasons widely unresolved. We have generated mice with a systemic impairment of oxidative phosphorylation (OXPHOS) due to aP2 cre-mediated targeted disruption, and unexpectedly ubiquitous reduction of mitochondrial frataxin protein expression. Only when maintained on a high-calorie diet resembling Westernized eating habits, these animals accumulate additional body fat, leading to increased body mass, and develop diabetes mellitus, despite the fact that both calorie uptake and physical activity were identical to that in control animals. This phenotype is caused by a mild but significant reduction in total energy expenditure paralleled by increased expression of ATP citrate lyase, a rate-limiting step in de novo synthesis of fatty acids and triglycerides. Taken together, these findings indicate that a limited impairment in oxidative metabolism within the mitochondria directly predisposes mammals to excessive body weight gain.
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition, D-14558 Potsdam-Rehbrücke, Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Pomplun
authors.forename: Anja
authors.initials: A
authors.lastname: Voigt
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Schulz
authors.forename: René
authors.initials: R
authors.lastname: Thierbach
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: Michael
authors.initials: M
authors.lastname: Ristow
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D015151:Immunoblotting; D007328:Insulin / Q000097:blood; D033862:Iron-Binding Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D000096923:Frataxin
chemical_list: D001275:ATP Citrate (pro-S)-Lyase; D007328:Insulin; D033862:Iron-Binding Proteins; D000096923:Frataxin