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A MED13-dependent skeletal muscle gene program controls systemic glucose homeostasis and hepatic metabolism.
Amoasii, Leonela; Holland, William; Sanchez-Ortiz, Efrain; Baskin, Kedryn K; Pearson, Mackenzie; Burgess, Shawn C; Nelson, Benjamin R; Bassel-Duby, Rhonda; Olson, Eric N.
Afiliação
  • Amoasii L; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research
  • Holland W; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
  • Sanchez-Ortiz E; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research
  • Baskin KK; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research
  • Pearson M; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
  • Burgess SC; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
  • Nelson BR; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research
  • Bassel-Duby R; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research
  • Olson EN; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research
Genes Dev ; 30(4): 434-46, 2016 Feb 15.
Article em En | MEDLINE | ID: mdl-26883362
The Mediator complex governs gene expression by linking upstream signaling pathways with the basal transcriptional machinery. However, how individual Mediator subunits may function in different tissues remains to be investigated. Through skeletal muscle-specific deletion of the Mediator subunit MED13 in mice, we discovered a gene regulatory mechanism by which skeletal muscle modulates the response of the liver to a high-fat diet. Skeletal muscle-specific deletion of MED13 in mice conferred resistance to hepatic steatosis by activating a metabolic gene program that enhances muscle glucose uptake and storage as glycogen. The consequent insulin-sensitizing effect within skeletal muscle lowered systemic glucose and insulin levels independently of weight gain and adiposity and prevented hepatic lipid accumulation. MED13 suppressed the expression of genes involved in glucose uptake and metabolism in skeletal muscle by inhibiting the nuclear receptor NURR1 and the MEF2 transcription factor. These findings reveal a fundamental molecular mechanism for the governance of glucose metabolism and the control of hepatic lipid accumulation by skeletal muscle. Intriguingly, MED13 exerts opposing metabolic actions in skeletal muscle and the heart, highlighting the customized, tissue-specific functions of the Mediator complex.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Músculo Esquelético / Complexo Mediador / Glucose / Homeostase / Fígado Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Músculo Esquelético / Complexo Mediador / Glucose / Homeostase / Fígado Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article