Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease.
Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway's IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD.
Department of Laboratory Animal Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea.
Sokho
S
Kim
Laboratory of Pathology, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea.
Surim
S
Park
Laboratory of Pathology, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea.
Bumseok
B
Kim
Department of Laboratory Animal Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea.
Jungkee
J
Kwon
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D000077271:Imiquimod; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism*
D000634:Aminoquinolines; D005231:Fatty Acids, Unsaturated; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D000077271:Imiquimod