Triiodothyronine enhances accumulation of intracellular lipids in adipocytes through thyroid hormone receptor α via direct and indirect mechanisms

• T3 induces the accumulation of intracellular lipids in 3T3-L1 cells.
• TRα was dominantly expressed in 3T3-L1 cells.
• T3 enhanced the FAS gene expression through direct binding of TRα.
• T3 lowered the lipolysis in 3T3-L1 cells.
• T3 reduced binding of T3-decreased SREBP-1c to the HSL promoter.

Triiodothyronine (T3) enhanced the expression of adipogenic and lipogenic genes with elevation of the intracellular lipids through thyroid hormone receptor (TR) α in mouse 3T3-L1 cells. However, the transcription of the SREBP-1c and HSL genes was decreased by T3. Such T3-mediated alterations were negated by TRα siRNA. Chromatin immunoprecipitation assay showed that the binding of TRα to the TR-responsive element (TRE) of the FAS promoter was elevated by T3. In contrast, the ability of TRα to bind to the TRE of the SREBP-1c promoter was decreased by T3. In addition, the binding of SREBP-1c to the SRE of the HSL promoter was lowered by T3. These results indicate that T3 increased the accumulation of intracellular lipids by enhancing the expression of the FAS gene through direct binding of TRα to the FAS promoter and simultaneously lowered the amount of lipolysis via reduced binding of T3-decreased SREBP-1c to the HSL promoter.