Journal
ANNUAL REVIEW OF NUTRITION
Volume 28, Issue -, Pages 13-33Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev.nutr.28.061807.155357
Keywords
basal metabolic rate; mitochondria; proton leak; uncouplers; uncoupling protein; coupling efficiency; rimonabant; sibutramine
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Funding
- NSERC of Canada
- Canadian Institutes of Health Research
- Institute of Nutrition, Metabolism and Diabetes
- Medical Research Council
- The Wellcome Trust
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We assess the existence, mechanism, and functions of less-than-maximal coupling efficiency of mitochondrial oxidative phosphorylation and its potential as a target for future antiobesity interventions. Coupling efficiency is the proportion of oxygen consumption used to make adenosine triphosphate (ATP) and do useful work. High coupling efficiency may lead to fat deposition; low coupling efficiency to a decrease in fat stores. We review obligatory and facultative energy expenditure and the role of a futile cycle of proton pumping and proton leak across the mitochondrial inner membrane in dissipating energy. Basal proton conductance is catalyzed primarily by the adenine nucleotide translocase but can be mimicked by chemical uncouplers. Inducible proton conductance is catalyzed by specific uncoupling proteins. We discuss the opportunities and pitfalls of targeting these processes as a treatment for obesity by decreasing coupling efficiency and increasing energy expenditure, either directly or through central mechanisms of energy homeostasis.
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