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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.

  1. S Brun,
  2. M C Carmona,
  3. T Mampel,
  4. O Viñas,
  5. M Giralt,
  6. R Iglesias and
  7. F Villarroya
  1. Department of Biochemistry and Molecular Biology, University of Barcelona, Spain.
    Diabetes 1999 Jun; 48(6): 1217-1222. https://doi.org/10.2337/diabetes.48.6.1217
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    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.

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    June 1999, 48(6)
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    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, F Villarroya
    Diabetes Jun 1999, 48 (6) 1217-1222; DOI: 10.2337/diabetes.48.6.1217

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    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, F Villarroya
    Diabetes Jun 1999, 48 (6) 1217-1222; DOI: 10.2337/diabetes.48.6.1217
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