Gut microbiota and serum metabolomic changes in Nogo-B knockout NAFLD mice
Background Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide.As a potential therapeutic target,Nogo-B is needed to determine whether it has an impact on the intestinal microbiome and metabolic pathways.Objective To explore the protective effect of Nogo-B knockdown on NAFLD and clarify the effects of Nogo-B knockdown on gut microbiota and serum metabolites in NAFLD mice.Methods Twelve 8-week-old wild type(WT)mice were randomly divided into WT-NCD group and WT-HFD group.Twelve 8-week-old Nogo-B knockout(Nogo-B-/-)mice were randomly divided into Nogo-B-/--NCD group and Nogo-B-/--HFD group.Mice in the WT-HFD and Nogo-B-/--HFD groups were fed with 60 kal%high-fat diet(HFD)for 12 weeks to construct the NAFLD mouse model,while mice in the WT-NCD and Nogo-B-/--NCD groups were fed with normal chow diet(NCD)for the same amount of time.Body weight was measured in all four groups.The hepatic triglyceride(TG)and total cholesterol(TC)levels were measured by enzyme-linked immunosorbent assay(ELISA);hematoxylin-eosin(HE)staining was used to evaluate the hepatic pathological features of mice in the four groups;and the gut microbiota and sera metabolites were examined in mice of the WT-HFD and the Nogo-B-/--HFD groups.Results At the end of 12-week modeling,the body weight and TC and TG levels in liver tissues of mice in the WT-HFD group were elevated compared with mice in the WT-NCD group(P＜0.01);and the body weight and TC and TG levels in liver tissues of mice in the Nogo-B-/--HFD group were also elevated compared with those of mice in the Nogo-B-/--NCD group(P＜0.01);whereas when the Nogo-B was knockout,the body weight and TC and TG levels in liver tissues of mice in the Nogo-B-/--HFD group decreased compared with those in the WT-HFD group(P＜0.01);intestinal microbiomics showed that Butyricicoccaceae became the dominant species in the gut microbes of Nogo-B knockdown NAFLD mice;serum metabolomics showed that 159 different metabolites were screened between the two groups(WT-HFD group,Nogo-B-/--HFD group),79 were up-regulated and 80 were down-regulated,and the metabolic pathways that were extremely significantly enriched(P＜0.001)were the citrate cycle/tricarboxylic acid cycle(TCA cycle),etc.,and the major enriched metabolites were citric acid,succinic acid,isocitrate and malic acid.Conclusion NAFLD mice with Nogo-B knockout show reduced hepatic lipid accumulation,increased beneficial intestinal microbiota,and improved metabolic disorders to some extent.Nogo-B may be a potential target for NAFLD therapy.
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