Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean - PubMed (original) (raw)

. 2000 Jul 27;406(6794):415-8.

doi: 10.1038/35019082.

J R Arch, H Chapman, A Haynes, C Lister, G B Moore, V Piercy, S A Carter, I Lehner, S A Smith, L J Beeley, R J Godden, N Herrity, M Skehel, K K Changani, P D Hockings, D G Reid, S M Squires, J Hatcher, B Trail, J Latcham, S Rastan, A J Harper, S Cadenas, J A Buckingham, M D Brand, A Abuin

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

J C Clapham et al. Nature. 2000.

Abstract

Uncoupling protein-3 (UCP-3) is a recently identified member of the mitochondrial transporter superfamily that is expressed predominantly in skeletal muscle. 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 metabolism. 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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