L-CARNITINE SUPPLEMENTATION ATTENUATES NAFLD PROGRESSION AND COMPLICATIONS IN A METHIONINE AND CHOLINE DEFICIENT DIET MOUSE MODEL

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and become one of the most common causes of chronic liver disease over the last decade in developed countries. The general prevalence of NAFLD is reported ranging between 20\u201330 % and 87 % in obese people. It is commonly associated with visceral obesity, type 2 diabetes mellitus, dyslipidemia and hypertension, all components of the metabolic syndrome, so that NAFLD might be considered an additional component of metabolic syndrome itself. As the rate of obesity, diabetes, and metabolic syndrome continue to increase, NAFLD will bring a tremendous impact on health care in the upcoming years. The underlying causes of the disease progression in NAFLD are unclear. Recent evidences suggest the development of lipid droplets (steatosis), subsequent generation of reactive oxygen species (ROS) and fibrosis deposition in the progression to non-alcoholic steatohepatitis (NASH). Moreover, continued elucidation has needed to understand fibrosis progression and regression. The paradigm of hepatic stellate cell (HSCs) activation remains the foundation for defining key translational challenges in order to accelerate the development of new therapies for patients with chronic liver disease. L-Carnitine (LCARN) is an essential nutrient that converts fat into energy in mitochondria. LCARN plays an important role in lipid metabolism; it acts as an essential cofactor for the \u3b2-oxidation of fatty acids. Very recently, LCARN has been proposed for the treatment of various diseases, including liver injury and several studies have shown that LCARN administration can ameliorate or prevent liver damage of various etiologies. We investigated the potential antioxidant and antifibrotic role of LCARN supplementation on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6 mice. Mice were divided into three groups of CONTR (normal diet without any treatment), MCDD (MCD diet only), MCDD+LCARN 200 mg/kg/die group. Liver and heart weight, histological changes and fibrosis progression were assessed after 6 weeks of experiments. The MCD-diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the MCDD+LCARN group. LCARN supplementation showed a role in controlling liver ROS generation and consequently coordinating the HSCs activation. Additionally, the same antioxidant and antifibrotic effect was observed in the myocardium. In conclusion, our findings indicate that LCARN has a potential role in control NAFLD progression to NASH. Therefore, our data suggest that LCARN may acts as a novel and potent supplementation agent against NAFLD cardiac complications