Open Access

Inhibition of JNK suppresses autophagy and attenuates insulin resistance in a rat model of nonalcoholic fatty liver disease

  • Authors:
    • Hua Yan
    • Yanqiong Gao
    • Ying Zhang
  • View Affiliations

  • Published online on: November 24, 2016     https://doi.org/10.3892/mmr.2016.5966
  • Pages: 180-186
  • Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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January-2017
Volume 15 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yan H, Gao Y and Zhang Y: Inhibition of JNK suppresses autophagy and attenuates insulin resistance in a rat model of nonalcoholic fatty liver disease. Mol Med Rep 15: 180-186, 2017.
APA
Yan, H., Gao, Y., & Zhang, Y. (2017). Inhibition of JNK suppresses autophagy and attenuates insulin resistance in a rat model of nonalcoholic fatty liver disease. Molecular Medicine Reports, 15, 180-186. https://doi.org/10.3892/mmr.2016.5966
MLA
Yan, H., Gao, Y., Zhang, Y."Inhibition of JNK suppresses autophagy and attenuates insulin resistance in a rat model of nonalcoholic fatty liver disease". Molecular Medicine Reports 15.1 (2017): 180-186.
Chicago
Yan, H., Gao, Y., Zhang, Y."Inhibition of JNK suppresses autophagy and attenuates insulin resistance in a rat model of nonalcoholic fatty liver disease". Molecular Medicine Reports 15, no. 1 (2017): 180-186. https://doi.org/10.3892/mmr.2016.5966