Abstract
Lifestyle-related diseases have become a major issue in recent years. The increasing incidence of fatty liver underlines the urgency with which the issues of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) need to be addressed. L-carnitine is a compound known to transport fatty acids into the mitochondria to enhance β-oxidation-mediated metabolism of fats. In this study, the effects of L-carnitine administration on fatty liver of medaka (Oryzias latipes) were analysed, to check for disease improvement and metabolic changes. Additionally, the effects of the concomitant administration of L-carnitine and eicosapentaenoic acid (20:5n-3) (EPA) were investigated. Findings indicated reduced lipid deposition, increase in metabolites associated with β-oxidation, and significant reduction in fatty acid levels in the liver, implying improvement in fatty liver condition. Concomitant administration of L-carnitine and EPA resulted in further benefits, via changes in fatty acid composition in the medaka fatty liver model.
Highlights
L-carnitine, a compound known to be involved in lipid metabolism, is synthesized from lysine and methionine mainly in the liver, with the involvement of vitamin C, ferrous ions, and niacin
nonalcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) involving steatohepatitis that is pathologically characterized by macrovesicular lipid deposition, ballooning degeneration of hepatocytes, infiltration of inflammatory cells, and perivenular or pericellular fibrosis around the central venous area
Xia et al reported that L-carnitine supplements improved the fatty liver in type 2 diabetic mice, and that the increase in fatty acid oxidation and decrease in the L-carnitine/Actyl- L-carnitine ratio are important[12]
Summary
L-carnitine, a compound (molecular weight: 161.21 kDa) known to be involved in lipid metabolism, is synthesized from lysine and methionine mainly in the liver, with the involvement of vitamin C, ferrous ions, and niacin. Since the inner mitochondrial membrane is impermeable to acyl-CoA on its own, fatty acyl-CoA on the outer mitochondrial membrane binds to L-carnitine through the action of carnitine acyl transferase I enzyme to temporarily generate fatty acyl carnitine This complex is capable of passing through the inner membrane via the acyl-carnitine/carnitine transporter, following which the fatty acyl group is translocated from L-carnitine to coenzyme A present within the mitochondria by carnitine acyltransferase II enzyme. Free L-carnitine is translocated back to the intermembrane space via the acyl-carnitine/carnitine transporter, available for the binding of a new fatty-acyl-CoA molecular. In this manner, L-carnitine contributes to fat transport and oxidation within the cell[2]. The medaka possesses an ability to hibernate, has high prolificacy, grows rapidly, is omnivorous and possesses carbohydrate/lipid metabolism functions similar to those found in mammals[5]
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