Linalool Mitigated High-Fat Diet-Induced Non-alcoholic Fatty Liver Disease by Regulating the Intestinal-Hepatic Axis via TGF-β/NF-kB/TLR4/ZO-1 Pathway

Non-alcoholic fatty liver disease is a persistent state and frequently accompanied by inflammation and disruption of the energy balance at the cellular and molecular levels. In this investigation, we tested the hypothesis that linalool may prevent high-fat diet-induced non-alcoholic fatty liver disease by regulating the intestinal-hepatic axis. Administration of linalool to rats with high- fat diet-induced non-alcoholic fatty liver disease for 45 days orally and the impact on insulin resistance and dyslipidemic markers in both blood and liver were estimated. Additionally, mRNA expression of occludin and zonula occludens-1 in the intestine and the mRNA expressions and levels of inflammatory cytokine (transforming growth factor-beta 1 (TGF-beta 1), tumor necrosis factor-a, and nuclear factor-kappa B (NF-kappa B)) in the hepatic tissue and secreted immunoglobulin A in intestinal tissues were examined. According to the findings of this investigation, linalool could be capable of alleviating insulin resistance and anomalies in lipid homeostasis. Additionally, it was shown that linalool effectively suppressed the production of inflammatory cytokines, considerably increased secreted IgA levels, and enhanced the mRNA expressions of occludin and zonula occludens-1 in the intestine. Hence, this study concludes that linalool might be able to ameliorate non-alcoholic fatty liver disease via regulation of the intestinal-hepatic axis through regulation of TGF-beta 1/NF-kappa B/ TLR4/ ZO-1 pathway.