RRC ID 54772
著者 Fang C, Cai X, Hayashi S, Hao S, Sakiyama H, Wang X, Yang Q, Akira S, Nishiguchi S, Fujiwara N, Tsutsui H, Sheng J.
タイトル Caffeine-stimulated muscle IL-6 mediates alleviation of non-alcoholic fatty liver disease.
ジャーナル Biochim Biophys Acta Mol Cell Biol Lipids
Abstract Caffeine intake is associated with a reduced risk developing non-alcoholic fatty liver disease (NAFLD), but the underlying molecular mechanisms remain to be fully elucidated. We report here that caffeine markedly improved high fat diet-induced NAFLD in mice resulting in a 10-fold increase in circulating IL-6 levels, leading to STAT3 activation in the liver. Interestingly, the expression of IL-6 mRNA was not increased in the liver, but increased substantially in the muscles of caffeine-treated mice. Caffeine was found to stimulate IL-6 production in cultured myotubes but not in hepatocytes, adipocytes, or macrophages. The inhibition of p38/MAPK abrogated caffeine-induced IL-6 production in muscle cells. Caffeine failed to improve NAFLD in IL-6 and hepatocyte-specific STAT3 knockout mice, indicating that the IL-6/STAT3 pathway is vital for the hepatoprotective effects of caffeine in NAFLD. The possibility that IL-6/STAT3-mediated hepatic autophagosome induction and hepatocytic oxygen consumption are involved in the anti-NAFLD effects of caffeine cannot be excluded, based on the findings presented here. Our results reveal that caffeine ameliorates NAFLD via crosstalk between muscle IL-6 production and liver STAT3 activation.
巻・号 1864(3)
ページ 271-280
公開日 2019-3-1
DOI 10.1016/j.bbalip.2018.12.003
PII S1388-1981(18)30370-6
PMID 30553055
MeSH Adipocytes / metabolism Animals Caffeine / metabolism Caffeine / pharmacology* Diet, High-Fat Disease Models, Animal Hepatocytes / metabolism Interleukin-6 / metabolism* Interleukin-6 / physiology Lipid Metabolism / physiology Liver / drug effects Liver / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Muscle, Skeletal / drug effects Muscle, Skeletal / metabolism Non-alcoholic Fatty Liver Disease / metabolism* Non-alcoholic Fatty Liver Disease / physiopathology STAT3 Transcription Factor / metabolism Signal Transduction / drug effects
IF 4.402
引用数 3
リソース情報
ヒト・動物細胞 C2C12(RCB0987)