Conjugated linoleic acid ameliorates hepatic steatosis by modulating intestinal permeability and gut microbiota in ob/ob mice

BACKGROUND: Conjugated linoleic acid (CLA) is an effective supplement for reducing fat mass, but its effect on hepatic steatosis remains controversial. OBJECTIVE: This study aims to evaluate the effect of CLA on liver fat accumulation, inflammation, gut microbiome, and intestinal barrier integrity. DESIGN: Wild-type (WT) mice and ob/ob (OB) mice were randomly divided into four groups according to the treatment with/without 1% CLA: WT, WT mice treated with CLA (WT-CLA), OB, and OB mice treated with CLA (OB-CLA). Lipid metabolism and hepatic fat accumulation were evaluated by changes in histological and biochemical parameters. Gene expressions related to liver inflammation and intestinal barrier integrity were examined. The effect of CLA on the gut microbiota population was investigated. RESULTS: The body weight, fatty tissue mass, and serum lipid levels of the WT-CLA group and OB-CLA group were separately lower than those of the WT group and OB group, but the livers of the WT-CLA group had more fatty lipids, higher triglyceride properties, and saturated fatty acid (FA) composition than those of the WT group, which was contrary to the effect of CLA on OB mice. Real time quantitative PCR results showed that CLA increased hepatic inflammation and intestinal permeability in the WT mice, while it significantly decreased the mRNA expression of liver TNF-α, IFN-γ, and IL-1β and markedly ameliorated intestinal tight junction proteins in the OB mice. The gut microbiota testing indicated a higher abundance of beneficial bacteria (e.g., Lachnoclostridium, Roseburia, Dubosiella, Oscillibacter, and Anaerostipes) and a lower abundance of pro-inflammatory bacteria (e.g., Tyzzerella and Alistipes) in the OB-CLA group than those of the OB group. Correlation analysis suggested that gut microbiota correlated with liver inflammation, intestinal permeability, and hepatic FA composition. CONCLUSION: CLA potentially contributed to ameliorating hepatic steatosis in OB mice via modulating liver inflammation, intestinal permeability, and gut microbiota, which suggests CLA is more suitable for people with obesity or overweight.