Activators of peroxisome proliferator-activated receptor-alpha induce the expression of the uncoupling protein-3 gene in skeletal muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 6; pp. 1217 - 1222
• Main Authors: BRUN, S, CARMONA, M. C, MAMPEL, T, VINAS, O, GIRALT, M, IGLESIAS, R, VILLARROYA, F
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-06-1999
• Subjects: Animals; Bezafibrate - pharmacology; Biological and medical sciences; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Clofibrate - pharmacology; DNA-Binding Proteins - metabolism; Eating; Fatty Acids, Nonesterified - blood; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Hypolipidemic Agents - pharmacology; Ion Channels; Leptin; Male; Mice; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - metabolism; Mitochondrial Proteins; Muscle Development; Muscle, Skeletal - drug effects; Muscle, Skeletal - growth & development; Peroxisome Proliferators - pharmacology; Proteins - genetics; Proteins - pharmacology; Pyrimidines - pharmacology; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Cytoplasmic and Nuclear - metabolism; Recombinant Proteins - pharmacology; RNA, Messenger - metabolism; Rosiglitazone; Striated muscle. Tendons; Thiazoles - pharmacology; Thiazolidinediones; Transcription Factors - agonists; Transcription Factors - metabolism; Transcriptional Activation; Uncoupling Protein 3; Vertebrates: osteoarticular system, musculoskeletal system; Vertebrata; Mammalia; Uncoupling protein; Mouse; Newborn animal; Rodentia; Gene expression; Striated muscle; Postnatal development; Peroxisome proliferator; Biological receptor
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.6.1217

Activators of peroxisome proliferator-activated receptor-alpha induce the expression of the uncoupling protein-3 gene in skeletal
muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth.
S Brun ,
M C Carmona ,
T Mampel ,
O Viñas ,
M Giralt ,
R Iglesias and
F Villarroya
Department of Biochemistry and Molecular Biology, University of Barcelona, Spain.
Abstract
The recently identified uncoupling protein-3 (UCP-3) gene, predicted to encode a new member of the family of uncoupling proteins,
is preferentially expressed in skeletal muscle and has been related to phenotypes of obesity and type 2 diabetes. We have
established that during mouse ontogeny, the expression of the UCP-3 gene is switched on in skeletal muscle just after birth.
The induction of UCP-3 gene expression is dependent on the initiation of suckling and particularly on lipid intake. Treatment
of newborn mice with activators of peroxisome proliferator-activated receptors (PPARs), such as clofibrate, bezafibrate, or
(4-chloro-6-(2,3-xylidine)-pirimidinylthio)acetic acid (WY 14,643), mimics the action of food intake on UCP-3 gene expression.
The specific ligand of PPAR-alpha WY 14,643 induces UCP-3 gene expression in a time- and dose-dependent manner, whereas the
thiazolidinedione BRL 49653, specific for PPAR-gamma, has no effect. These treatments act without altering circulating free
fatty acids. During development, skeletal muscle expresses constitutive levels of PPAR-delta mRNA, whereas expression of the
PPAR-gamma gene is undetectable. PPAR-alpha gene expression is developmentally regulated in muscle as it is first expressed
at birth, just before UCP-3 gene induction occurs. The induction of UCP-3 gene expression by WY 14,643 is impaired in skeletal
muscle of premature neonates, which do not express PPAR-alpha. It is proposed that the UCP-3 gene is predominantly regulated
in neonatal muscle by PPAR-alpha activation.