Effects of Tithonia diversifolia (Hemsl.) A. Gray extract on adipocyte differentation of human mesenchymal stem cells

Introduction: Clinical and experimental data suggested the importance of olive oil rich diet as potential nutritional strategy able to prevent obesity and related disorders including non-alcoholic fatty liver disease (NAFLD). The beneficial and protective effects of the olive oil, one of the most important component of the mediterranean diet, havebeen attributed largely to the hydroxytyrosol, the major metabolite of the polyphenol oleuropein [1]. Aim:The potential mechanisms of action of polyphenols in NAFLD are still largely unexplored. To this purpose, we used an experimental model of steatosis, feeding young rats with a high fat diet (HFD) rich in usaturated and saturated fats and treating them with hydroxytyrosol. This type of diet is used as nutritional model to induce insulinresistance (IR) and NAFLD in non-genetically modified animals [2]. Materials and methods: In our experiment, we administered HFD for 6 weeks to induce the early events of NAFLD due to fat overnutrition in young animals to exclude age and gender influences. After weaning, male SpragueDawley rats were divided into three groups as following: 1) a control group receiving the standard diet (STD; 10.5% fat, 16.4% proteins, and 73.1% carbohydrates; 4.06Kcal/g); 2) a HFD fed group receiving vehicle (HFD; 58.0% fat, 16.4% protein, and 25.5 carbohydrates; 5.6 kcal/g); and 3) HFDfed rats treated by gavage with hydroxytyrosol (HFD+HT, 10 mg/kg/die) [3]. After 5 weeks all rats were subjected to the oral glucose tolerance test (OGTT). After 6 weeks blood sample was collected by cardiac puncture and serum obtained. Liver tissue was excised and immediately frozen for following determinations. Results:HFD rats showed a marked increase in serum AST, ALT and cholesterol. Fasting glucose levels were strongly increased, and this parameter was associated to an impairment of glucose tolerance. Hepatic damage, inflammation and oxidative stress were assessed by evaluation of pro-inflammatory cytokines (TNF-α and IL-6), reactive oxygen species (ROS) production and malondialdehyde (MDA) levels. In HFDfed rats hydroxytyrosol treatment reduced serum parameters of hepatic damage and showed an euglycaemic effect in fasting rats and in OGTT. Moreover, the treatment with this polyphenolic compound reduced liver inflammation and oxidative stress decreasing the transcriptional levels of TNF- α and IL-6, and the production of ROS and MDA. Finally, hydroxytyrosol treatment was able to ameliorate hepatic functionality preventing nitrosylation of liver proteins and restoring PPAR- α mRNA amount. Conclusions: Our data demonstrate a protective effect of hydroxytyrosol in preventing and limiting the early inflammatory events responsible of insulin-resistance and steatosis onset. In particular, this oleuropein derivative was able to reduce hepatic inflammation and oxidative damage and to restore glucose homeostasis. So, we can conclude that beneficial effects of mediterranean diet assumption might be, at least in part, related to hydroxytyrosol presence in olive oil. Indeed, consumption of olive oil enriched in hydroxytyrosol could be considered an available strategy to prevent liver steatosis and its related complications. References 1. Hur W et al., Nutr Res. 2012;32:778-86 2. Mattace Raso G et al., PLoS One. 2013;8:e68626 3. Ristagno G et al., J Agric Food Chem. 2012;60:5859-65