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Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8182-7. doi: 10.1073/pnas.1608987113. Epub 2016 Jul 5.

Insulin induction of SREBP-1c in rodent liver requires LXRα-C/EBPβ complex.

Author information

1
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
2
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 Joe.Goldstein@UTSouthwestern.edu mike.brown@utsouthwestern.edu.

Abstract

Insulin increases lipid synthesis in liver by activating transcription of the gene encoding sterol regulatory element-binding protein-1c (SREBP-1c). SREBP-1c activates the transcription of all genes necessary for fatty acid synthesis. Insulin induction of SREBP-1c requires LXRα, a nuclear receptor. Transcription of SREBP-1c also requires transcription factor C/EBPβ, but a connection between LXRα and C/EBPβ has not been made. Here we show that LXRα and C/EBPβ form a complex that can be immunoprecipitated from rat liver nuclei. Chromatin immunoprecipitation assays showed that the LXRα-C/EBPβ complex binds to the SREBP-1c promoter in a region that contains two binding sites for LXRα and is known to be required for insulin induction. Knockdown of C/EBPβ in fresh rat hepatocytes or mouse livers in vivo reduces the ability of insulin to increase SREBP-1c mRNA. The LXRα-C/EBPβ complex is bound to the SREBP-1c promoter in the absence or presence of insulin, indicating that insulin acts not by increasing the formation of this complex, but rather by activating it.

KEYWORDS:

chromatin immunoprecipitation; fasting and refeeding; fatty acid synthesis; rat hepatocytes; transcription

PMID:
27382175
PMCID:
PMC4961151
DOI:
10.1073/pnas.1608987113
[Indexed for MEDLINE]
Free PMC Article

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