Liver Lipidomics Analysis Revealed the Novel Ameliorative Mechanisms of L-Carnitine on High-Fat Diet-Induced NAFLD Mice

Abstract

The beneficial effects of L-carnitine on non-alcoholic fatty liver disease (NAFLD) were revealed in previous reports. However, the underlying mechanisms remain unclear. In this study, we established a high fat diet (HFD)-induced NAFLD mice model and systematically explored the effects and mechanisms of dietary L-carnitine supplementation (0.2% to 4%) on NAFLD. A lipidomics approach was conducted to identify specific lipid species involved in the ameliorative roles of L-carnitine in NAFLD. Compared with a normal control group, the body weight, liver weight, concentrations of TG in the liver and serum AST and ALT levels were dramatically increased by HFD feeding (p < 0.05), accompanied with obvious liver damage and the activation of the hepatic TLR4/NF-κB/NLRP3 inflammatory pathway. L-carnitine treatment significantly improved these phenomena and exhibited a clear dose-response relationship. The results of a liver lipidomics analysis showed that a total of 12 classes and 145 lipid species were identified in the livers. Serious disorders in lipid profiles were noticed in the livers of the HFD-fed mice, such as an increased relative abundance of TG and a decreased relative abundance of PC, PE, PI, LPC, LPE, Cer and SM (p < 0.05). The relative contents of PC and PI were significantly increased and that of DG were decreased after the 4% L-carnitine intervention (p < 0.05). Moreover, we identified 47 important differential lipid species that notably separated the experimental groups based on VIP ≥ 1 and p < 0.05. The results of a pathway analysis showed that L-carnitine inhibited the glycerolipid metabolism pathway and activated the pathways of alpha-linolenic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and Glycosylphosphatidylinositol (GPI)-anchor biosynthesis. This study provides novel insights into the mechanisms of L-carnitine in attenuating NAFLD.