title: Toll-like receptor-4 signalling in the progression of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet in mice.
abstract: The aim of the present study was to investigate Toll-like receptor-4 (TLR4) signalling at different stages of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat, high-fructose (HFHFr) diet in mice. Both TLR4 wild-type (WT) and mutant (TLR4(mut) ) mice were fed either standard chow (SC) or the HFHFr 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 HFHFr. Expression of TLR4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor (IRF) 3 and IRF7 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 TLR4(mut) mice fed the HFHFr diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHFr diet increased at Week 16. The data suggest that TLR4 signalling mediates non-alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD.
authors.affiliation: Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Zhen-Jie
authors.initials: ZJ
authors.lastname: Zhuang
authors.forename: Dong-Xue
authors.initials: DX
authors.lastname: Bian
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Ma
authors.forename: Yun-Hao
authors.initials: YH
authors.lastname: Xun
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Yin-Lan
authors.initials: YL
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Jia
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Zhu
authors.forename: De-Wei
authors.initials: DW
authors.lastname: Ye
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Lou
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Shi
mesh_terms: D028341:Activins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity*; D019422:Dietary Sucrose / Q000008:administration & dosage / Q000633:toxicity*; D005632:Fructose / Q000008:administration & dosage / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced* / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D019422:Dietary Sucrose; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C422405:activin A; D028341:Activins; D005632:Fructose
keywords: mice; non-alcoholic fatty liver disease; toll -like receptor 4