Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean |
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Authors: | Clapham J C Arch J R Chapman H Haynes A Lister C Moore G B Piercy V Carter S A Lehner I Smith S A Beeley L J Godden R J Herrity N Skehel M Changani K K Hockings P D Reid D G Squires S M Hatcher J Trail B Latcham J Rastan S Harper A J Cadenas S Buckingham J A Brand M D Abuin A |
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Affiliation: | Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. JohnvClapham-1@sbphrd.com |
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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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