title: Direct effects of iodothyronines on excess fat storage in rat hepatocytes.
abstract: OBJECTIVE
  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-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.
  
  
  RESULTS
  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.
  
  
  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.
authors.affiliation: Dipartimento di Biologia, Università di Genova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Grasselli
authors.forename: Adriana
authors.initials: A
authors.lastname: Voci
authors.forename: Laura
authors.initials: L
authors.lastname: Canesi
authors.forename: Rita
authors.initials: R
authors.lastname: De Matteis
authors.forename: Fernando
authors.initials: F
authors.lastname: Goglia
authors.forename: Federica
authors.initials: F
authors.lastname: Cioffi
authors.forename: Emilia
authors.initials: E
authors.lastname: Fugassa
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gallo
authors.forename: Laura
authors.initials: L
authors.lastname: Vergani
mesh_terms: D042962:Acyl-CoA Oxidase / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004104:Diiodothyronines / Q000494:pharmacology*; D005234:Fatty Liver / Q000378:metabolism / Q000517:prevention & control; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D065626:Non-alcoholic Fatty Liver Disease; D019301:Oleic Acid / Q000008:administration & dosage; D047493:PPAR alpha / Q000235:genetics; D047494:PPAR delta / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D010168:Palmitates / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D004104:Diiodothyronines; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D010168:Palmitates; D012333:RNA, Messenger; D014284:Triiodothyronine; D019301:Oleic Acid; C030103:3,5-diiodothyronine; D002374:Catalase; D013482:Superoxide Dismutase; D042962:Acyl-CoA Oxidase