Involvement of resistin-like molecule ? in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice.

ABSTRACT: Resistin-like molecule ? (RELM?) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELM? to non-alcoholic steatohepatitis (NASH) development. First, RELM? knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELM? and that RELM? expression levels in the colon and the numbers of RELM?-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELM?-KO mice to distinguish between the contributions of RELM? in these two organs. These experiments revealed the requirement of RELM? in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELM?-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELM? in the gut and Kupffer cells to NASH development, raising the possibility of RELM? being a novel therapeutic target for NASH.

SUBMITTER: Okubo H 

PROVIDER: S-EPMC4730188 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature