title: Insulin induction of SREBP-1c in rodent liver requires LXRα-C/EBPβ complex.
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.
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 Joe.Goldstein@UTSouthwestern.edu mike.brown@utsouthwestern.edu.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Goldstein
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 Joe.Goldstein@UTSouthwestern.edu mike.brown@utsouthwestern.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Brown
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D000071518:Liver X Receptors / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D007328:Insulin; D000071518:Liver X Receptors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051780:Sterol Regulatory Element Binding Protein 1
keywords: chromatin immunoprecipitation; fasting and refeeding; fatty acid synthesis; rat hepatocytes; transcription