title: Rapamycin improves palmitate-induced ER stress/NF κ B pathways associated with stimulating autophagy in adipocytes.
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.
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors: Jiajing
authors: J
authors: Yin
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors: Liping
authors: L
authors: Gu
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors: Yufan
authors: Y
authors: Wang
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors: Nengguang
authors: N
authors: Fan
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors: Yuhang
authors: Y
authors: Ma
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors: Yongde
authors: Y
authors: Peng
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D010168:Palmitates / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D015850:Interleukin-6; D010168:Palmitates; D002738:Chloroquine; D020123:Sirolimus
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