Effects of Indoleamine 2,3-Dioxygenase Deficiency on High-Fat Diet-Induced Hepatic Inflammation

Junji Nagano, Masahito Shimizu, Takeshi Hara, Yohei Shirakami, Takahiro Kochi, Nobuhiko Nakamura, Hirofumi Ohtaki, Hiroyasu Ito, Takuji Tanaka, Hisashi Tsurumi, Kuniaki Saito, Mitsuru Seishima, Hisataka Moriwaki

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Hepatic immune regulation is associated with the progression from simple steatosis to non-alcoholic steatohepatitis, a severe condition of inflamed fatty liver. Indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme that mediates the catabolism of L-tryptophan to L-kynurenine, plays an important role in hepatic immune regulation. In the present study, we examined the effects of IDO gene silencing on high-fat diet (HFD)-induced liver inflammation and fibrosis in mice. After being fed a HFD for 26 weeks, the IDO-knockout (KO) mice showed a marked infiltration of inflammatory cells, especially macrophages and T lymphocytes, in the liver. The expression levels of F4/80, IFNγ, IL-1β, and IL-6 mRNA in the liver and the expression levels of F4/80 and TNF-α mRNA in the white adipose tissue were significantly increased in IDO-KO mice, although hepatic steatosis, the accumulation of intrahepatic triglycerides, and the amount of oxidative stress were lower than those in IDO-wild-type mice. IDO-KO mice also developed marked pericellular fibrosis in the liver, accumulated hepatic hydroxyproline, and exhibited increased expression levels of hepatic TGF-β1 mRNA. These findings suggest that IDO-KO renders the mice more susceptible to HFD-induced hepatic inflammation and fibrosis. Therefore, IDO may have a protective effect against hepatic fibrosis, at least in this HFD-induced liver injury model.

Original languageEnglish
Article numbere73404
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - 09-09-2013
Externally publishedYes

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Indoleamine-Pyrrole 2,3,-Dioxygenase
High Fat Diet
high fat diet
Nutrition
inflammation
Fats
Liver
Inflammation
liver
Knockout Mice
mice
liver cirrhosis
fatty liver
Messenger RNA
fibrosis
Fatty Liver
Liver Cirrhosis
Kynurenine
kynurenine
Fibrosis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Nagano, J., Shimizu, M., Hara, T., Shirakami, Y., Kochi, T., Nakamura, N., ... Moriwaki, H. (2013). Effects of Indoleamine 2,3-Dioxygenase Deficiency on High-Fat Diet-Induced Hepatic Inflammation. PLoS One, 8(9), [e73404]. https://doi.org/10.1371/journal.pone.0073404
Nagano, Junji ; Shimizu, Masahito ; Hara, Takeshi ; Shirakami, Yohei ; Kochi, Takahiro ; Nakamura, Nobuhiko ; Ohtaki, Hirofumi ; Ito, Hiroyasu ; Tanaka, Takuji ; Tsurumi, Hisashi ; Saito, Kuniaki ; Seishima, Mitsuru ; Moriwaki, Hisataka. / Effects of Indoleamine 2,3-Dioxygenase Deficiency on High-Fat Diet-Induced Hepatic Inflammation. In: PLoS One. 2013 ; Vol. 8, No. 9.
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Nagano, J, Shimizu, M, Hara, T, Shirakami, Y, Kochi, T, Nakamura, N, Ohtaki, H, Ito, H, Tanaka, T, Tsurumi, H, Saito, K, Seishima, M & Moriwaki, H 2013, 'Effects of Indoleamine 2,3-Dioxygenase Deficiency on High-Fat Diet-Induced Hepatic Inflammation', PLoS One, vol. 8, no. 9, e73404. https://doi.org/10.1371/journal.pone.0073404

Effects of Indoleamine 2,3-Dioxygenase Deficiency on High-Fat Diet-Induced Hepatic Inflammation. / Nagano, Junji; Shimizu, Masahito; Hara, Takeshi; Shirakami, Yohei; Kochi, Takahiro; Nakamura, Nobuhiko; Ohtaki, Hirofumi; Ito, Hiroyasu; Tanaka, Takuji; Tsurumi, Hisashi; Saito, Kuniaki; Seishima, Mitsuru; Moriwaki, Hisataka.

In: PLoS One, Vol. 8, No. 9, e73404, 09.09.2013.

Research output: Contribution to journalArticle

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AU - Hara, Takeshi

AU - Shirakami, Yohei

AU - Kochi, Takahiro

AU - Nakamura, Nobuhiko

AU - Ohtaki, Hirofumi

AU - Ito, Hiroyasu

AU - Tanaka, Takuji

AU - Tsurumi, Hisashi

AU - Saito, Kuniaki

AU - Seishima, Mitsuru

AU - Moriwaki, Hisataka

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Nagano J, Shimizu M, Hara T, Shirakami Y, Kochi T, Nakamura N et al. Effects of Indoleamine 2,3-Dioxygenase Deficiency on High-Fat Diet-Induced Hepatic Inflammation. PLoS One. 2013 Sep 9;8(9). e73404. https://doi.org/10.1371/journal.pone.0073404