title: Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice.
abstract: Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ 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 RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ 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 RELMβ-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 RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH.
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Okubo
authors.affiliation: Institute for Adult Disease, Asahi Life Foundation, 2-2-6, Bakuro-cho, Chuo-ku, Tokyo 103-0002, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakatsu
authors.affiliation: Department of Molecular and Cellular Biology, Kobe Pharma Research Institute, Nippon Boehringer-Ingelheim Co. Ltd. 6-7-5, Minatoshimaminami-cho, Chuo-ku, Kobe city, Hyogo 650-0047, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Iizuka
authors.affiliation: Department of Molecular and Cellular Biology, Kobe Pharma Research Institute, Nippon Boehringer-Ingelheim Co. Ltd. 6-7-5, Minatoshimaminami-cho, Chuo-ku, Kobe city, Hyogo 650-0047, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taki
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo.
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kamata
authors.affiliation: Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nagamachi
authors.affiliation: Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inaba
authors.affiliation: Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
authors.forename: Fusanori
authors.initials: F
authors.lastname: Nishimura
authors.affiliation: Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd. 5-11, Izumi, Kunitachi-shi, 186-8650 Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Asahara
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd. 5-11, Izumi, Kunitachi-shi, 186-8650 Tokyo, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd. 5-11, Izumi, Kunitachi-shi, 186-8650 Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Chonan
authors.affiliation: Department of Molecular and Cellular Biology, Kobe Pharma Research Institute, Nippon Boehringer-Ingelheim Co. Ltd. 6-7-5, Minatoshimaminami-cho, Chuo-ku, Kobe city, Hyogo 650-0047, Japan.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Encinas
authors.affiliation: Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima Japan.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
mesh_terms: D000818:Animals; D015415:Biomarkers; D002796:Choline Deficiency; D003106:Colon / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome; D005786:Gene Expression Regulation; D006729:Hormones, Ectopic / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; C486522:Retnlb protein, mouse; D051197:Toll-Like Receptor 4; D008715:Methionine
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