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

TitleMice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean.
Publication TypeJournal Article
Year of Publication2000
AuthorsClapham, JC, Arch, JR, Chapman, H, Haynes, A, Lister, C, Moore, GB, Piercy, V, Carter, SA, Lehner, I, Smith, SA, Beeley, LJ, Godden, RJ, Herrity, N, Skehel, M, Changani, KK, Hockings, PD, Reid, DG, Squires, SM, Hatcher, J, Trail, B, Latcham, J, Rastan, S, Harper, AJ, Cadenas, S, Buckingham, JA, Brand, MD, Abuin, A
JournalNature
Volume406
Issue6794
Pagination415-8
Date Published2000 Jul 27
ISSN0028-0836
KeywordsAdipose Tissue, Animals, Animals, Genetically Modified, Blood Glucose, Carrier Proteins, Energy Metabolism, Female, Humans, Hyperphagia, Ion Channels, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL, Mitochondria, Mitochondrial Proteins, Muscle, Skeletal, Phenotype, Thinness, Uncoupling Protein 3
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.

DOI10.1038/35019082
Alternate JournalNature
Citation Key10.1038/35019082
PubMed ID10935638