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Acta Physiologica 2011; Volume 203, Supplement 688
The 62nd National Congress of the Italian Physiological Society
9/25/2011-9/27/2011
Sorrento, Italy
OLEIC ACID BUT NOT FRUCTOSE INDUCES STEATOSIS AND INSULIN RESISTANCE IN PRIMARY ADULT AND FETAL HEPATOCYTES: PREVENTIVE EFFECT OF 3,5-T2
Abstract number: O28
GNOCCHI1 D, LEONI1 S, BRUSCALUPI1 G
1Dept Biology and Biotechnology "Charles Darwin", "Sapienza" Univ., Rome, Italy
Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging pathology, becoming very frequent in industrialized countries, due to an excess of fats and/or fructose in the diet, together with poor physical activity. Aim of this work is to define an in vitro model of NAFLD, to test pathogenic mechanisms and potentially therapeutic molecules. We treated adult and fetal rat hepatocytes in primary culture with oleic acid and/or fructose for 24 h and examined their effects on lipid accumulation and cell viability, and on the levels of some proteins involved in insulin signaling pathway. Moreover, we tested the effect of 3,5-Diiodotyronine (3,5-T2) in preventing and reverting lipid accumulation. Results show that oleic acid is a potent inducer of fat accumulation, both in adult and fetal hepatocytes, whereas fructose is able to do so only at very high concentrations; oleic acid has no effect on cell viability, while is toxic on fetal cells. Furthermore, oleic acid upregulates the expression of at least two proteins of insulin signaling pathway (p85 regulatory subunit of PI3K and PTEN), differently from fructose. These modifications can be related to the induction of hepatic insulin resistance, that is characteristic of NAFLD.
Therefore, we used these hepatocytes to test the effect of 3,5-T2, showing that this metabolite of 3,5,3'-Triiodotyronine (T3), considered devoid of generalized toxic effects, is able to prevent and revert lipid accumulation in adult, but not in fetal cells.
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Acta Physiologica 2011; Volume 203, Supplement 688 :O28