In chick embryo hepatocytes, activation of acetyl-CoA carboxylase-α (ACCα) transcription by 3,5,3′-triiodothyronine (T3) is mediated by a cis-acting regulatory unit (−101 to −71 bp) that binds the nuclear T3 receptor (TR) and sterol regulatory element-binding protein-1 (SREBP-1). SREBP-1 directly interacts with TR on the ACCα gene to enhance T3-induced transcription. Here, we show that treating hepatocytes with T3 or insulin stimulates a 4-fold increase in the concentration of the mature, active form of SREBP-1. When T3 and insulin are added together, a 7-fold increase in the mature SREBP-1 concentration is observed. Time course studies indicate that the T3-induced increase in mature SREBP-1 abundance is closely associated with changes in ACCα transcription and that the mechanism mediating the effect of T3 on mature SREBP-1 is distinct from that mediating the effect of insulin. Transfection analyses indicate that inhibition of ACCα transcription by cAMP or hexanoate is mediated by ACCα sequences between −101 and −71 bp. Treatment with cAMP or hexanoate suppresses the increase in mature SREBP-1 abundance caused by T3 and insulin. These results establish a new interaction between the SREBP-1 and TR signaling pathways and provide evidence that SREBP-1 plays an active role in mediating the effects of T3, insulin, cAMP, and hexanoate on ACCα transcription.
Digital Commons Citation
Zhang, Yanqiao; Yin, Liya; and Hillgartner, F Bradley, "SREBP-1 integrates the actions of thyroid hormone, insulin, cAMP, and medium-chain fatty acids on ACCalpha transcription in hepatocytes" (2002). Faculty & Staff Scholarship. 342.
Zhang, Yanqiao., Yin, Liya., & Hillgartner, F Bradley. (2002). Srebp-1 Integrates The Actions Of Thyroid Hormone, Insulin, Camp, And Medium-Chain Fatty Acids On Accalpha Transcription In Hepatocytes. The Journal of Lipid Research, 44(2), 356-35668. http://doi.org/10.1194/jlr.M200283-JLR200