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

JC Clapham, JRS Arch, H Chapman, A Haynes… - Nature, 2000 - nature.com
JC Clapham, JRS Arch, H Chapman, A Haynes, C Lister, GBT Moore, V Piercy, SA Carter…
Nature, 2000nature.com
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 …
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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