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Toll‐like receptor‐4 signalling in the progression of non‐alcoholic fatty liver disease induced by high‐fat and high‐fructose diet in mice
Author(s) -
Liu Jing,
Zhuang Zhenjie,
Bian Dongxue,
Ma Xiaojie,
Xun Yunhao,
Yang Wenjun,
Luo Yan,
Liu Yinlan,
Jia Ling,
Wang Yan,
Zhu Mingli,
Ye Dewei,
Zhou Gang,
Lou Guoqiang,
Shi Junping
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12241
Subject(s) - steatohepatitis , endocrinology , fatty liver , medicine , fibrosis , tlr4 , steatosis , inflammation , fructose , biology , irf7 , receptor , biochemistry , innate immune system , disease
Summary The aim of the present study was to investigate Toll‐like receptor‐4 ( TLR 4) signalling at different stages of non‐alcoholic fatty liver disease ( NAFLD ) induced by a high‐fat, high‐fructose ( HFHF r) diet in mice. Both TLR 4 wild‐type ( WT ) and mutant ( TLR 4 mut ) mice were fed either standard chow ( SC ) or the HFHF r diet for different periods of time from 4 to 16 weeks. Pathological characteristics and function of the liver were assessed. Simple steatosis, steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in WT mice fed with the HFHF r. Expression of TLR 4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor ( IRF ) 3 and IRF 7 started to increase at Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This pattern was consistent with changes in inflammation in the liver revealed by haematoxylin and eosin staining. However, lipid accumulation, inflammation and fibrosis in livers of TLR 4 mut mice fed the HFHF r diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHF r diet increased at Week 16. The data suggest that TLR 4 signalling mediates non‐alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD .