title: Treatment of experimental non-alcoholic steatohepatitis by targeting α7 nicotinic acetylcholine receptor-mediated inflammatory responses in mice.
abstract: Non‑alcoholic fatty liver disease (NAFLD) is one of the most common types of liver disease, affecting up to 30% of the general population worldwide. Non‑alcoholic steatohepatitis (NASH) is a severe form of NAFLD without any effective therapies available. The present study showed that activation of α7‑nicotinic acetylcholine receptor (α7 nAChR) may be a novel potential strategy for NASH therapy. Treatment with the α7 nAChR agonist nicotine for three weeks obviously attenuated hepatic steatosis in a high-fat diet‑induced mouse model of NASH. Investigation of the underlying mechanism showed that nicotine reduced the secretion of the pro‑inflammatory cytokines tumor necrosis factor α and interleukin 6 in vitro and in vivo. Inflammation is an integral part of NASH and is the most prevalent form of hepatic pathology found in the general population; therefore, the effect of α7 nAChR activation against NASH may be ascribed to its anti‑inflammatory effects. In addition, the present study showed that nicotine‑stimulated α7 nAChR activation led to a significant downregulation of nuclear factor kappa B (NK‑κB) and extracellular signal-regulated kinase (ERK). It therefore appeared that activation of α7 nAChR suppressed the production of pro‑inflammatory cytokines through NK‑κB and ERK pathways. In conclusion, the present study indicated that targeting α7 nAChR may represent a novel treatment strategy for NASH.
authors.affiliation: Department of Anesthesiology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Digestive Diseases, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Infectious Disease, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Chen
authors.affiliation: Department of Infectious Disease, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Tong
authors.affiliation: Department of Intensive Care Unit, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Ding
authors.affiliation: Department of Infectious Disease, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
authors.forename: Cui-Lan
authors.initials: CL
authors.lastname: Tang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015850:Interleukin-6 / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009538:Nicotine / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D016328:NF-kappa B; D018722:Nicotinic Agonists; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine