The mitochondrial uncoupling protein (UCP) in the mitochondrial inner membrane of mammalian brown adipose tissue generates heat by uncoupling oxidative phosphorylation1. This process protects against cold2 and regulates energy balance3. Manipulation of thermogenesis could be an effective strategy against obesity4–9. Here we determine the role of UCP in the regulation of body mass by targeted inactivation of the gene encoding it. We find that UCP-deficient mice consume less oxygen after treatment with a β3-adrenergic-receptor agonist and that they are sensitive to cold, indicating that their thermo-regulation is defective. However, this deficiency caused neither hyperphagia nor obesity in mice fed on either a standard or a high-fat diet. We propose that the loss of UCP may be compensated by UCP2, a newly discovered homologue of UCP; this gene is ubiquitously expressed and is induced in the brown fat of UCP-deficient mice.
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Enerbäck, S., Jacobsson, A., Simpson, E. et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387, 90–94 (1997). https://doi.org/10.1038/387090a0
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