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Hepatic GATA4 regulates cholesterol and triglyceride homeostasis in collaboration with LXRs.
Bideyan, Lara; López Rodríguez, Maykel; Priest, Christina; Kennelly, John P; Gao, Yajing; Ferrari, Alessandra; Rajbhandari, Prashant; Feng, An-Chieh; Tevosian, Sergei G; Smale, Stephen T; Tontonoz, Peter.
Afiliação
  • Bideyan L; Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, USA.
  • López Rodríguez M; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, USA.
  • Priest C; Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, USA.
  • Kennelly JP; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, USA.
  • Gao Y; Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, USA.
  • Ferrari A; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, USA.
  • Rajbhandari P; Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, USA.
  • Feng AC; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, USA.
  • Tevosian SG; Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, USA.
  • Smale ST; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, USA.
  • Tontonoz P; Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, USA.
Genes Dev ; 36(21-24): 1129-1144, 2022.
Article em En | MEDLINE | ID: mdl-36522129
ABSTRACT
GATA4 is a transcription factor known for its crucial role in the development of many tissues, including the liver; however, its role in adult liver metabolism is unknown. Here, using high-throughput sequencing technologies, we identified GATA4 as a transcriptional regulator of metabolism in the liver. GATA4 expression is elevated in response to refeeding, and its occupancy is increased at enhancers of genes linked to fatty acid and lipoprotein metabolism. Knocking out GATA4 in the adult liver (Gata4LKO) decreased transcriptional activity at GATA4 binding sites, especially during feeding. Gata4LKO mice have reduced plasma HDL cholesterol and increased liver triglyceride levels. The expression of a panel of GATA4 binding genes involved in hepatic cholesterol export and triglyceride hydrolysis was down-regulated in Gata4LKO mice. We further demonstrate that GATA4 collaborates with LXR nuclear receptors in the liver. GATA4 and LXRs share a number of binding sites, and GATA4 was required for the full transcriptional response to LXR activation. Collectively, these results show that hepatic GATA4 contributes to the transcriptional control of hepatic and systemic lipid homeostasis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Nucleares Órfãos / Fígado Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Nucleares Órfãos / Fígado Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article