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

John C. Clapham (), Jonathan R. S. Arch, Helen Chapman, Andrea Haynes, Carolyn Lister, Gary B. T. Moore, Valerie Piercy, Sabrina A. Carter, Ines Lehner, Stephen A. Smith, Lee J. Beeley, Robert J. Godden, Nicole Herrity, Mark Skehel, K. Kumar Changani, Paul D. Hockings, David G. Reid, Sarah M. Squires, Jonathan Hatcher, Brenda Trail, Judy Latcham, Sohaila Rastan, Alexander J. Harper, Susana Cadenas, Julie A. Buckingham, Martin D. Brand and Alejandro Abuin
Additional contact information
John C. Clapham: Departments of Vascular Biology
Jonathan R. S. Arch: Departments of Vascular Biology
Helen Chapman: Departments of Vascular Biology
Andrea Haynes: Departments of Vascular Biology
Carolyn Lister: Departments of Vascular Biology
Gary B. T. Moore: Departments of Vascular Biology
Valerie Piercy: Departments of Vascular Biology
Sabrina A. Carter: Departments of Vascular Biology
Ines Lehner: Departments of Vascular Biology
Stephen A. Smith: Departments of Vascular Biology
Lee J. Beeley: Bioinformatics
Robert J. Godden: Molecular Biology
Nicole Herrity: Gene Expression Sciences
Mark Skehel: Bioanalytical Sciences
K. Kumar Changani: Departments of Safety Assessment
Paul D. Hockings: Departments of Safety Assessment
David G. Reid: Departments of Safety Assessment
Sarah M. Squires: Departments of Safety Assessment
Jonathan Hatcher: Neurobehavioiural Research
Brenda Trail: Neurobehavioiural Research
Judy Latcham: Laboratory Animal Sciences
Sohaila Rastan: SmithKline Beecham Pharmaceuticals
Alexander J. Harper: Neurobehavioiural Research
Susana Cadenas: University of Cambridge
Julie A. Buckingham: University of Cambridge
Martin D. Brand: University of Cambridge
Alejandro Abuin: SmithKline Beecham Pharmaceuticals

Nature, 2000, vol. 406, issue 6794, 415-418

Abstract: 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.

Date: 2000
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DOI: 10.1038/35019082

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