Il-19 contributes to the development of nonalcoholic steatohepatitis by altering lipid metabolism

Yasu Taka Azuma, Takashi Fujita, Takeshi Izawa, Kana Hirota, Kazuhiro Nishiyama, Airi Ikegami, Tomoko Aoyama, Mikihito Ike, Yumi Ushikai, Mitsuru Kuwamura, Hideki Fujii, Koichi Tsuneyama

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Abstract

Interleukin (IL)-19, a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. Nonalcoholic steatohepatitis (NASH) is a disease that has progressed from nonalcoholic fatty liver disease (NAFLD) and is characterized by inflammation and fibrosis. We evaluated the functions of IL-19 in a NAFLD/NASH mouse model using a 60% high fat diet with 0.1% methionine, without choline, and with 2% cholesterol (CDAHFD). Wild-type (WT) and IL-19 gene-deficient (KO) mice were fed a CDAHFD or standard diet for 9 weeks. Liver injury, inflammation, and fibrosis induced by CDAHFD were significantly worse in IL-19 KO mice than in WT mice. IL-6, TNF-α, and TGF-β were significantly higher in IL-19 KO mice than in WT mice. As a mechanism using an in vitro experiment, palmitate-induced triglyceride and cholesterol contents were decreased by the addition of IL-19 in HepG2 cells. Furthermore, addition of IL-19 decreased the expression of fatty acid synthesis-related enzymes and increased ATP content in HepG2 cells. The action of IL-19 in vitro suppressed lipid metabolism. In conclusion, IL-19 may play an important role in the development of steatosis and fibrosis by directly regulating liver metabolism and may be a potential target for the treatment of liver diseases.

Original languageEnglish
Article number3513
JournalCells
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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