Rapamycin Improves Palmitate-Induced ER Stress-NFκB Pathways Associated with Stimulating Autophagy in AdipocytesReport as inadecuate




Rapamycin Improves Palmitate-Induced ER Stress-NFκB Pathways Associated with Stimulating Autophagy in Adipocytes - Download this document for free, or read online. Document in PDF available to download.

Mediators of Inflammation - Volume 2015 2015, Article ID 272313, 12 pages -

Research ArticleDepartment of Endocrinology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China

Received 20 October 2014; Revised 17 December 2014; Accepted 17 December 2014

Academic Editor: Luca Cantarini

Copyright © 2015 Jiajing Yin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Obesity-induced endoplasmic reticulum ER stress and inflammation lead to adipocytes dysfunction. Autophagy helps to adapt to cellular stress and involves in regulating innate inflammatory response. In present study, we examined the activity of rapamycin, a mTOR kinase inhibitor, against endoplasmic reticulum stress and inflammation in adipocytes. An in vitro model was used in which 3T3-L1 adipocytes were preloaded with palmitate PA to generate artificial hypertrophy mature adipocytes. Elevated autophagy flux and increased number of autophagosomes were observed in response to PA and rapamycin treatment. Rapamycin attenuated PA-induced PERK and IRE1-associated UPR pathways, evidenced by decreased protein levels of eIF2α phosphorylation, ATF4, CHOP, and JNK phosphorylation. Inhibiting autophagy with chloroquine CQ exacerbated these ER stress markers, indicating the role of autophagy in ameliorating ER stress. In addition, cotreatment of CQ abolished the anti-ER stress effects of rapamycin, which confirms the effect of rapamycin on ERs is autophagy-dependent. Furthermore, rapamycin decreased PA-induced nuclear translocation of NFκB P65 subunit, thereby NFκB-dependent inflammatory cytokines MCP-1 and IL-6 expression and secretion. In conclusion, rapamycin attenuated PA-induced ER stress-NFκB pathways to counterbalance adipocytes stress and inflammation. The beneficial of rapamycin in this context partly depends on autophagy. Stimulating autophagy may become a way to attenuate adipocytes dysfunction.





Author: Jiajing Yin, Liping Gu, Yufan Wang, Nengguang Fan, Yuhang Ma, and Yongde Peng

Source: https://www.hindawi.com/



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