Background & Aims: Previous studies have demonstrated that 3,5-L-diiodothyronine (T2) 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 T2 on the liver has not been elucidated. In this study, we investigated the ability of T2 to reduce the excess lipids in isolated hepatocytes treated with fatty acids (FFAs). The effects of T2 were compared with those elicited by 3,30,5-L-triiodothyronine (T3). 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 T2 or T3. Lipid content, morphometry of lipid droplets (LDs), and expression of the adipocyte differentiation-related protein (ADRP) and the peroxisome proliferator-activated receptors (PPAR-a, -c, -d) 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-c, and PPAR-d/b mRNAs, as well as in the activities of AOX, SOD, and CAT. The addition of T2 or T3 to ‘‘fatty hepatocytes’’ resulted in a reduction in: (i) lipid content and LD diameter; (ii) PPAR-c and PPAR-d expression; (iii) activities of AOX and antioxidant enzymes. Conclusions: These data demonstrate, for the first time, a direct action of both T2 and T3 in reducing the excess fat in cultured hepatocytes.

Direct effects of iodothyronines on excess fat storage in rat hepatocytes.

DE MATTEIS, RITA;
2011

Abstract

Background & Aims: Previous studies have demonstrated that 3,5-L-diiodothyronine (T2) 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 T2 on the liver has not been elucidated. In this study, we investigated the ability of T2 to reduce the excess lipids in isolated hepatocytes treated with fatty acids (FFAs). The effects of T2 were compared with those elicited by 3,30,5-L-triiodothyronine (T3). 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 T2 or T3. Lipid content, morphometry of lipid droplets (LDs), and expression of the adipocyte differentiation-related protein (ADRP) and the peroxisome proliferator-activated receptors (PPAR-a, -c, -d) 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-c, and PPAR-d/b mRNAs, as well as in the activities of AOX, SOD, and CAT. The addition of T2 or T3 to ‘‘fatty hepatocytes’’ resulted in a reduction in: (i) lipid content and LD diameter; (ii) PPAR-c and PPAR-d expression; (iii) activities of AOX and antioxidant enzymes. Conclusions: These data demonstrate, for the first time, a direct action of both T2 and T3 in reducing the excess fat in cultured hepatocytes.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11576/2512451
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