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

Hirofumi Okubo, Akifumi Kushiyama, Hideyuki Sakoda, Yusuke Nakatsu, Masaki Iizuka, Naoyuki Taki, Midori Fujishiro, Toshiaki Fukushima, Hideaki Kamata, Akiko Nagamachi, Toshiya Inaba, Fusanori Nishimura, Hideki Katagiri, Takashi Asahara, Yasuto Yoshida, Osamu Chonan, Jeffery Encinas, Tomoichiro Asano

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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.

Original languageEnglish
Article number20157
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Jan 28 2016

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Resistin
Fatty Liver
Choline
Methionine
Diet
Kupffer Cells
Knockout Mice
Lipopolysaccharides
Radiation Chimera
Serum
Lactic Acid
Colon

All Science Journal Classification (ASJC) codes

  • General

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Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice. / Okubo, Hirofumi; Kushiyama, Akifumi; Sakoda, Hideyuki; Nakatsu, Yusuke; Iizuka, Masaki; Taki, Naoyuki; Fujishiro, Midori; Fukushima, Toshiaki; Kamata, Hideaki; Nagamachi, Akiko; Inaba, Toshiya; Nishimura, Fusanori; Katagiri, Hideki; Asahara, Takashi; Yoshida, Yasuto; Chonan, Osamu; Encinas, Jeffery; Asano, Tomoichiro.

In: Scientific reports, Vol. 6, 20157, 28.01.2016.

Research output: Contribution to journalArticle

Okubo, H, Kushiyama, A, Sakoda, H, Nakatsu, Y, Iizuka, M, Taki, N, Fujishiro, M, Fukushima, T, Kamata, H, Nagamachi, A, Inaba, T, Nishimura, F, Katagiri, H, Asahara, T, Yoshida, Y, Chonan, O, Encinas, J & Asano, T 2016, 'Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice', Scientific reports, vol. 6, 20157. https://doi.org/10.1038/srep20157
Okubo, Hirofumi ; Kushiyama, Akifumi ; Sakoda, Hideyuki ; Nakatsu, Yusuke ; Iizuka, Masaki ; Taki, Naoyuki ; Fujishiro, Midori ; Fukushima, Toshiaki ; Kamata, Hideaki ; Nagamachi, Akiko ; Inaba, Toshiya ; Nishimura, Fusanori ; Katagiri, Hideki ; Asahara, Takashi ; Yoshida, Yasuto ; Chonan, Osamu ; Encinas, Jeffery ; Asano, Tomoichiro. / Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice. In: Scientific reports. 2016 ; Vol. 6.
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