Direct effects of iodothyronines on excess fat storage in rat hepatocytes

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)).

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-α, -γ, -δ) were evaluated. Activities of the lipolytic enzyme acyl CoA oxidase-AOX and the antioxidant enzymes superoxide dismutase-SOD and catalase-CAT were also determined.

FFA-induced lipid accumulation was associated with an increase in both number/size of LDs and expression of ADRP, PPAR-γ, and PPAR-δ/β 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-γ and PPAR-δ expression; (iii) activities of AOX and antioxidant enzymes.

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.