title: Inhibition of JNK suppresses autophagy and attenuates insulin resistance in a rat model of nonalcoholic fatty liver disease.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, the pathological process of which is complex. Activation of the c‑Jun N‑terminal kinase (JNK) signaling pathway is associated with the mechanism underlying obesity-induced insulin resistance. Furthermore, the JNK signaling pathway and dysfunctional autophagy serve important roles in hepatic lipid metabolism. However, the exact role of JNK in autophagy and obesity‑induced insulin resistance is not fully understood. Therefore, the present study aimed to investigate the underlying mechanisms by which the JNK signaling pathway regulates autophagy and insulin resistance in fatty liver. A rat model of NAFLD was established using a high‑fat diet (HFD), and insulin resistance in the livers of HFD rats was determined by peritoneal glucose tolerance testing. The results indicated that a HFD induced impaired glucose tolerance, liver function injury, insulin resistance and increased autophagy in rats. Treatment with SP600125, an inhibitor of JNK, relieved NAFLD in rats. Furthermore, SP600125 decreased the expression levels of autophagy-associated genes, including Beclin-1, microtubule-associated protein 1A/1B light chain 3, autophagy related gene (Atg)3 and Atg5, and the phosphorylation of insulin receptor (IR) β-subunit, IR substrate-1 and protein kinase B in vivo. In conclusion, JNK inhibition may suppress autophagy and attenuate insulin resistance. Therefore, JNK inhibition may provide a novel therapeutic strategy for the treatment of NAFLD.
authors.affiliation: Department of Gerontology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Functional Examination, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Gerontology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000627:therapeutic use*; D001343:Autophagy; D059305:Diet, High-Fat / Q000009:adverse effects; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley
chemical_list: D000873:Anthracenes; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D048055:Mitogen-Activated Protein Kinase 8