Tri-iodothyronine upregulates adiponutrin mRNA expression in rat and human adipocytes

Adiponutrin (PNPLA3) is expressed in adipose tissue. Although its precise function is unknown, some data suggest a dual role in lipid homeostasis. We have investigated the influence of thyroid hormone (TH) on PNPLA3 mRNA, in rat and human cultured white adipocytes and in rat white adipose tissue (WAT). Pnpla3 mRNA increased during differentiation of rat adipocytes in an insulin-dependent manner. Tri-iodothyronine further increased Pnpla3 expression at any day during differentiation and its effects were time and dose-dependent. The Pnpla3 mRNA half-life was stabilized by tri-iodothyronine, but a transcriptional component was also observed. Pnpla3 mRNA decreased in WAT of hypothyroid rats and was partially restored by treatment with TH. Taqman analysis showed that tri-iodothyronine also increased human PNPLA3 expression in cultured subcutaneous adipocytes from obese patients. In conclusion, PNPLA3 mRNA expression is upregulated by tri-iodothyronine in adipocytes in vitro, in humans and rats, and in vivo in rat WAT.