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

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 LXR alpha, a nuclear receptor. Transcription of SREBP-1c also requires transcription factor C/EBP beta, but a connection between LXR alpha and C/EBP beta has not been made. Here we show that LXR alpha and C/EBP beta form a complex that can be immunoprecipitated from rat liver nuclei. Chromatin immunoprecipitation assays showed that the LXR alpha-C/EBP beta complex binds to the SREBP-1c promoter in a region that contains two binding sites for LXR alpha and is known to be required for insulin induction. Knockdown of C/EBP beta in fresh rat hepatocytes or mouse livers in vivo reduces the ability of insulin to increase SREBP-1c mRNA. The LXR alpha-C/EBP beta 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.