Treatment of experimental non-alcoholic steatohepatitis by targeting α7 nicotinic acetylcholine receptor-mediated inflammatory responses in mice

• Published in: Molecular medicine reports Vol. 12; no. 5; pp. 6925 - 6931
• Main Authors: ZHOU, ZHOU, LIU, YING-CHAO, CHEN, XIAO-MEI, LI, FU-QIANG, TONG, XIAO-JUAN, DING, YUE-PING, TANG, CUI-LAN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.11.2015; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Acetylcholine receptors (nicotinic); alpha7 Nicotinic Acetylcholine Receptor - agonists; alpha7 Nicotinic Acetylcholine Receptor - immunology; Animals; Anti-Inflammatory Agents - therapeutic use; Cell Line; Cell receptors; Cellular control mechanisms; Cytokines; Development and progression; Diet, High-Fat - adverse effects; Drug dosages; Extracellular signal-regulated kinase; Fatty liver; FDA approval; Genetic aspects; Health aspects; High fat diet; Hypertension; Inflammation; Inflammation - drug therapy; Inflammation - immunology; Inflammation - pathology; Insulin; Interleukin 6; Interleukin-6 - immunology; Laboratory animals; Liver - drug effects; Liver - immunology; Liver - pathology; Liver cancer; Liver diseases; Male; Medical research; Metabolic pathways; Metabolic syndrome; Mice; NF-kappa B - immunology; Nicotine; Nicotine - therapeutic use; Nicotinic Agonists - therapeutic use; non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - immunology; Non-alcoholic Fatty Liver Disease - pathology; non-alcoholic steatohepatitis; nuclear factor kappa B; Steatosis; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; α7-nicotinic acetylcholine receptor; United States > US; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2015.4318

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.