The proton pump inhibition removes alcoholic fatty liver disease via inactivation of TLR signaling pathway

Abstract

Pathogenesis of alcoholic fatty liver disease has never been established. It has been that TLR‐signaling pathway plays an important role in the development. What primes TLR‐signaling pathway and any prevention remains unclear. The proton pump exists in endosome in macrophage. Endosome includes TLR4, TLR7 and TLR9, which may contribute to innate immune response in macrophage. We hypothesized that inhibition of proton pump reduces alcoholic fatty liver disease. To clarify the hypothesis, we evaluated fatty liver injury in alcohol‐fed rats after treatment with a proton pump inhibitor. Male Wistar rats were fed with Lieber‐DeCarli alcohol liquid diet for 4 weeks. Lansoprazol, a proton pump inhibitor, was treated to alcohol liquid diet‐fed rats. Immunohistochemical staining for TLR7 and TLR9 was performed in formalin‐fixed, paraffin‐embedded liver sections. ER stress markers were analyzed by quantitative real‐time PCR. Alcohol feeding caused expression of TLR7 and TLR9 and accumulation of ER stress. Inhibition of proton pump results in reduction of fatty liver change, especially lipid droplets in hepatocytes and no staining for TLR7 and TLR9. However, accumulation of ER stress was not changed by inhibition of proton pump. Therefore, chronic alcohol consumption causes developing fatty liver disease via TLR7 and TLR9, which expression can be reduced by inhibition of proton pump.