Metabolomics Study of Serum from a Chronic Alcohol-Fed Rat Model Following Administration of Defatted Tenebrio molitor Larva Fermentation Extract

Abstract

We have previously showed that defatted mealworm fermentation extract (MWF) attenuates alcoholic liver injury by regulating lipid, inflammatory, and antioxidant metabolism in chronic alcohol-fed rats. The current metabolomics study was performed to monitor biochemical events following the administration of MWF (daily for eight weeks) to a rat model of alcoholic liver injury by gas chromatography-tandem mass spectrometry (GC-MS/MS). The levels of 15 amino acids (AAs), 17 organic acids (OAs), and 19 free fatty acids (FFAs) were measured in serum. Analysis of variance (ANOVA), principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) were used to compare the levels of 51 metabolites in serum. In particular, 3-hydroxybutyric acid (3-HB), pyroglutamic acid (PG), octadecanoic acid, and docosahexaenoic acid (DHA) were evaluated as high variable importance point (VIP) scores and PCA loading scores as determined by PLS-DA and PCA, and these were significantly higher in the MWF and silymarin groups than in the EtOH group. MWF showed a protective effect from alcohol-induced liver damage by elevating hepatic β-oxidation activity, and serum 3-HB levels were significantly higher in the MWF group than in the EtOH control group. Glycine levels were higher in the MWF group than in the EtOH group, and PG levels (related to glutathione production) were also elevated, indicating a reduction in alcohol-related oxidative stress. In addition, MWF is protected from alcohol-induced inflammation and steatosis by increasing serum DHA, palmitic, and octadecanoic acid levels as compared with the EtOH group. These results suggest that MWF might attenuate alcoholic liver disease, due to its anti-inflammatory and antioxidant effects by up-regulating hepatic β-oxidation activity and down-regulating liver FFA uptake.