Reduced expression of mitochondrial frataxin in mice exacerbates diet-induced obesity
- 10 April 2007
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (15), 6377-6381
- https://doi.org/10.1073/pnas.0611631104
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.Keywords
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