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Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean

Abstract

Uncoupling protein-3 (UCP-3) is a recently identified member of the mitochondrial transporter superfamily1,2 that is expressed predominantly in skeletal muscle1,2. However, its close relative UCP-1 is expressed exclusively in brown adipose tissue, a tissue whose main function is fat combustion and thermogenesis. Studies on the expression of UCP-3 in animals and humans in different physiological situations support a role for UCP-3 in energy balance and lipid metabolism3,4. However, direct evidence for these roles is lacking. Here we describe the creation of transgenic mice that overexpress human UCP-3 in skeletal muscle. These mice are hyperphagic but weigh less than their wild-type littermates. Magnetic resonance imaging shows a striking reduction in adipose tissue mass. The mice also exhibit lower fasting plasma glucose and insulin levels and an increased glucose clearance rate. This provides evidence that skeletal muscle UCP-3 has the potential to influence metabolic rate and glucose homeostasis in the whole animal.

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Figure 1: Expression of human UCP-3 in mouse skeletal muscle.
Figure 2: Phenotype of male UCP-3tg mice.
Figure 3: MRI analysis of UCP-3tg mice.

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Acknowledgements

S.C. was supported by a Marie Curie (EC) fellowship.

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Correspondence to John C. Clapham.

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Clapham, J., Arch, J., Chapman, H. et al. Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 406, 415–418 (2000). https://doi.org/10.1038/35019082

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