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

被引：24

作者：

Okubo, Hirofumi ^{[1
]}

Kushiyama, Akifumi ^{[2
]}

Sakoda, Hideyuki ^{[3
]}

Nakatsu, Yusuke ^{[1
]}

Iizuka, Masaki ^{[4
]}

Taki, Naoyuki ^{[4
]}

Fujishiro, Midori ^{[3
]}

Fukushima, Toshiaki ^{[1
]}

Kamata, Hideaki ^{[1
]}

Nagamachi, Akiko ^{[5
,6
]}

Inaba, Toshiya ^{[5
,6
]}

Nishimura, Fusanori ^{[7
]}

Katagiri, Hideki ^{[8
]}

Asahara, Takashi ^{[9
]}

Yoshida, Yasuto ^{[9
]}

Chonan, Osamu ^{[9
]}

Encinas, Jeffery ^{[4
]}

Asano, Tomoichiro ^{[1
]}

机构：

[1] Hiroshima Univ, Grad Sch Med, Dept Med Sci, Minami Ku, 1-2-3 Kasumi, Hiroshima, Hiroshima, Japan

[2] Asahi Life Fdn, Inst Adult Dis, Chuo Ku, 2-2-6 Bakuro Cho, Tokyo 1030002, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Internal Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo, Japan

[4] Nippon Boehringer Ingelheim Co Ltd, Dept Mol & Cellular Biol, Kobe Pharma Res Inst, Chuo Ku, 6-7-5 Minatoshimaminami Cho, Kobe, Hyogo 6500047, Japan

[5] Hiroshima Univ, Dept Mol Oncol, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan

[6] Hiroshima Univ, Leukemia Program Project, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan

[7] Hiroshima Univ, Grad Sch Biomed Sci, Dept Dent Sci Hlth Promot, Div Cervicognathostomatol,Aoba Ku, 2-1 Seiryo Machi, Sendai, Miyagi, Japan

[8] Tohoku Univ, Grad Sch Med, Div Mol Metab & Diabet, Aoba Ku, 2-1 Seiryo Machi, Sendai, Miyagi 980, Japan

[9] Yakult Honsha Co Ltd, Yakult Cent Inst, 5-11 Izumi, Kunitachi, Tokyo 1868650, Japan

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

FATTY LIVER; MICROBIOTA; OBESITY; INFLAMMATION; RELM-BETA/FIZZ2; PERMEABILITY; SECRETION; ENDOTOXIN; PROTECTS; INNATE;

D O I：

10.1038/srep20157

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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

引用

页数：13

共 41 条

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