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

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

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 methio...

Full description

Bibliographic Details
Main Authors: 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
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730188/
id pubmed-4730188
recordtype oai_dc
spelling pubmed-47301882016-02-03 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 Article 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. Nature Publishing Group 2016-01-28 /pmc/articles/PMC4730188/ /pubmed/26818807 http://dx.doi.org/10.1038/srep20157 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author 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
spellingShingle 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
author_facet 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
author_sort Okubo, Hirofumi
title Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice
title_short Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice
title_full Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice
title_fullStr Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice
title_full_unstemmed Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice
title_sort involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice
description 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.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730188/
_version_ 1613529575948550144

Similar Items