Human Stearoyl-CoA Desaturase 1 (SCD-1) Gene Expression Is Negatively Regulated by Thyroid Hormone without Direct Binding of Thyroid Hormone Receptor to the Gene Promoter

Abstract

Stearoyl-CoA desaturase-1 (SCD-1) plays a pivotal role in an increase of triglyceride by an excess of dietary carbohydrate intake. Dietary carbohydrates increase SCD-1 gene expression in liver by sterol response element binding protein (SREBP)-1c-dependent and SREBP-1c -independent pathways. Previous report demonstrated that thyroid hormone (TH) negatively regulates mouse SCD-1 gene promoter before SREBP-1c was revealed. We reported that TH negatively regulates SREBP-1c recently. Therefore, in the current study, we examined whether and how TH regulates human SCD-1 gene expression and evaluated SREBP-1c effect on the negative regulation. Luciferase assays revealed that TH suppresses both mouse and human SCD-1 gene promoter activity. In SREBP-1 knockdown HepG2 cells, TH still suppresses SCD-1 gene promoter activity, and it also exerted the negative regulation under cotransfection of a small amount of SREBP-1c. These data indicated that SREBP-1c does not play the decisive role for the negative regulation by TH. The responsible region for the negative regulation in human SCD-1 gene promoter turned out to be between -124 and -92 bp, referred to as site A. Chromatin immunoprecipitation assays demonstrated that TH receptor-β is recruited to the region upon T(3) administration, although TR-β does not bind directly to site A. In conclusion, TH negatively regulates human SCD-1 gene expression in without direct binding of the TH receptor to the SCD-1 gene promoter.