title: 3,5-diiodo-l-thyronine, by modulating mitochondrial functions, reverses hepatic fat accumulation in rats fed a high-fat diet.
abstract: OBJECTIVE
  Mitochondrial dysfunction is central to the physiopathology of steatosis and/or non-alcoholic fatty liver disease. In this study on rats we investigated whether 3,5-diiodo-l-thyronine (T2), a biologically active iodothyronine, acting at mitochondrial level is able to reverse hepatic steatosis after its induction through a high-fat diet.
  
  
  METHODS
  Hepatic steatosis was induced by long-term high-fat feeding of rats for six weeks which were then fed the same high-fat diet for the next 4 weeks and were simultaneously treated or not treated with T2. Histological analyses were performed on liver sections (by staining with Sudan black B). In liver mitochondria fatty acid oxidation rate, mitochondrial efficiency (by measuring proton conductance) and mitochondrial oxidative stress (by measuring H(2)O(2) release, aconitase and SOD activity) were detected.
  
  
  RESULTS
  Stained sections showed that T2 treatment reduced hepatic fatty accumulation induced by a high-fat diet. At the mitochondrial level, the fatty acid oxidation rate and carnitine palmitoyl transferase activity were enhanced by T2 treatment. Moreover, by stimulating mitochondrial uncoupling, T2 caused less efficient utilization of fatty acid substrates and ameliorated mitochondrial oxidative stress.
  
  
  CONCLUSIONS
  These data demonstrate that T2, by activating mitochondrial processes, markedly reverses hepatic steatosis in vivo.
authors.affiliation: Department of Biological Sciences, University of Naples Federico II, Naples, Italy.
authors.forename: Maria Pina
authors.initials: MP
authors.lastname: Mollica
authors.forename: Lillà
authors.initials: L
authors.lastname: Lionetti
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno
authors.forename: Assunta
authors.initials: A
authors.lastname: Lombardi
authors.forename: Pieter
authors.initials: P
authors.lastname: De Lange
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.forename: Antonia
authors.initials: A
authors.lastname: Lanni
authors.forename: Gina
authors.initials: G
authors.lastname: Cavaliere
authors.forename: Antonio
authors.initials: A
authors.lastname: Barletta
authors.forename: Fernando
authors.initials: F
authors.lastname: Goglia
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D004104:Diiodothyronines / Q000008:administration & dosage / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D004041:Dietary Fats; D004104:Diiodothyronines; D008055:Lipids; C030103:3,5-diiodothyronine; D013972:Thyrotropin; D000410:Alanine Transaminase