Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean.
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.
Clapham
J C
JC
Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. JohnvClapham-1@sbphrd.com
Arch
J R
JR
Chapman
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H
Haynes
A
A
Lister
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C
Moore
G B
GB
Piercy
V
V
Carter
S A
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Lehner
I
I
Smith
S A
SA
Beeley
L J
LJ
Godden
R J
RJ
Herrity
N
N
Skehel
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M
Changani
K K
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Hockings
P D
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Reid
D G
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Squires
S M
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Hatcher
J
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Trail
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B
Latcham
J
J
Rastan
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Harper
A J
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Cadenas
S
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Buckingham
J A
JA
Brand
M D
MD
Abuin
A
A
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D006963:Hyperphagia / Q000235:genetics; D007473:Ion Channels; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000502:physiology*; D010641:Phenotype; D013851:Thinness; D000071247:Uncoupling Protein 3
D001786:Blood Glucose; D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604392:UCP3 protein, human; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3