Direct effects of iodothyronines on excess fat storage in rat hepatocytes

Background & Aims: Previous studies have demonstrated that 3,5-L-diiodothyronine (T-2) is able to prevent lipid accumulation in the liver of rats fed a high-fat diet. Whether this effect is due to a direct action of T-2 on the liver has not been elucidated. In this study, we investigated the ability of T-2 to reduce the excess lipids in isolated hepatocytes treated with fatty acids (FFAs). The effects of T-2 were compared with those elicited by 3,3',5-L-triiodothyronine (T-3). Methods: To mimic the fatty liver condition, primary cultures of rat hepatocytes were overloaded with lipids, by exposure to FFAs (fatty hepatocytes), and then treated with T-2 or T-3. Lipid content, morphometry of lipid droplets (LDs), and expression of the adipocyte differentiation-related protein (ADRP) and the peroxisome proliferator-activated receptors (PPAR-alpha, -gamma, -delta) were evaluated. Activities of the lipolytic enzyme acyl CoA oxidase - AOX and the antioxidant enzymes superoxide dismutase - SOD and catalase - CAT were also determined. Results: FFA-induced lipid accumulation was associated with an increase in both number/size of LDs and expression of ADRP, PPAR-gamma, and PPAR-delta/beta mRNAs, as well as in the activities of AOX, SOD, and CAT. The addition of T-2 or T-3 to fatty hepatocytes resulted in a reduction in: (i) lipid content and LD diameter; (ii) PPAR-gamma and PPAR-delta expression; (iii) activities of AOX and antioxidant enzymes. Conclusions: These data demonstrate, for the first time, a direct action of both T-2 and T-3 in reducing the excess fat in cultured hepatocytes. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.