研究業績

Resistin-like molecule beta (RELMbeta) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMbeta to non-alcoholic steatohepatitis (NASH) development. First, RELMbeta 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 RELMbeta and that RELMbeta expression levels in the colon and the numbers of RELMbeta-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMbeta-KO mice to distinguish between the contributions of RELMbeta in these two organs. These experiments revealed the requirement of RELMbeta 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 RELMbeta-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 RELMbeta in the gut and Kupffer cells to NASH development, raising the possibility of RELMbeta being a novel therapeutic target for NASH.