3,5-diiodo-l-thyronine, by modulating mitochondrial functions, reverses hepatic fat accumulation in rats fed a high-fat diet.
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.
Mollica
Maria Pina
MP
Department of Biological Sciences, University of Naples Federico II, Naples, Italy.
Lionetti
Lillà
L
Moreno
Maria
M
Lombardi
Assunta
A
De Lange
Pieter
P
Antonelli
Alessandro
A
Lanni
Antonia
A
Cavaliere
Gina
G
Barletta
Antonio
A
Goglia
Fernando
F
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
D004041:Dietary Fats; D004104:Diiodothyronines; D008055:Lipids; C030103:3,5-diiodothyronine; D013972:Thyrotropin; D000410:Alanine Transaminase