Rapamycin improves palmitate-induced ER stress/NF κ B pathways associated with stimulating autophagy in adipocytes.
Rapamycin improves palmitate-induced ER stress/NF κ B pathways associated with stimulating autophagy in adipocytes.
复制标题
雷帕霉素可改善棕榈酸诱导的 ER 应激/NF kappa B 通路，该通路与刺激脂肪细胞自噬相关。
DOI：
10.1155/2015/272313
复制
发表时间：
2015
影响因子：
4.6
通讯作者：
Peng Y
中科院分区：
文献类型：
--
作者：
Yin J;Gu L;Wang Y;Fan N;Ma Y;Peng Y
肥胖诱导的内质网（ER）应激和炎症导致脂肪细胞功能障碍。自噬有助于适应细胞应激，并参与调节先天性炎症反应。在本研究中，我们检测了雷帕霉素（一种mTOR激酶抑制剂）对脂肪细胞内质网应激和炎症的活性。使用体外模型，其中3 T3-L1脂肪细胞预载棕榈酸酯（PA）以产生人工肥大成熟脂肪细胞。PA和雷帕霉素处理后，自噬通量升高，自噬体数量增加。雷帕霉素减弱PA诱导的PERK和IRE 1相关UPR通路，表现为eIF 2 α磷酸化、ATF 4、CHOP和JNK磷酸化蛋白水平降低。用氯喹（CQ）抑制自噬加重了这些ER应激标志物，表明自噬在改善ER应激中的作用。此外，CQ的共处理消除了雷帕霉素的抗ER应激作用，这证实了雷帕霉素对ER的作用是自噬依赖的。此外，雷帕霉素还能降低PA诱导的NFκB B P65亚基核转位，从而抑制NFκ B依赖的炎症细胞因子MCP-1和IL-6的表达和分泌。总之，雷帕霉素减弱PA诱导的ER应激/NFκB通路，以平衡脂肪细胞应激和炎症。在这种情况下，雷帕霉素的益处部分取决于自噬。刺激自噬可能成为减轻脂肪细胞功能障碍的一种方法。
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.
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影响因子：
4.8
作者：
Jansen, H. J.;van Essen, P.;Stienstra, R.
通讯作者：
Stienstra, R.
影响因子：
4.8
作者：
Listenberger, LL;Ory, DS;Schaffer, JE
通讯作者：
Schaffer, JE
影响因子：
3.3
作者：
Jung, Chang Hwa;Jun, Chang Bong;Kim, Do-Hyung
通讯作者：
Kim, Do-Hyung
影响因子：
9
作者：
通讯作者：
--
巨噬细胞 mTORC1 破坏可减少肥胖小鼠的炎症和胰岛素抵抗
影响因子：
8.2
作者：
Jiang, Hongfeng;Westerterp, Marit;Ai, Ding
通讯作者：
Ai, Ding