BACKGROUND/AIMS: 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. CONCLUSION: These data demonstrate that T2, by activating mitochondrial processes, markedly reverses hepatic steatosis in vivo.
3,5-diiodo-l-thyronine, by modulating mitochondrial functions, reverses hepatic fat accumulation in rats fed a high-fat diet
LIONETTI, Lilla';
2009-01-01
Abstract
BACKGROUND/AIMS: 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. CONCLUSION: These data demonstrate that T2, by activating mitochondrial processes, markedly reverses hepatic steatosis in vivo.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
