Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: implications for apoptosis and inflammation.
Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: implications for apoptosis and inflammation.
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棕榈酸诱导成熟脂肪细胞内质网应激和自噬：对细胞凋亡和炎症的影响。
DOI：
10.3892/ijmm.2015.2085
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发表时间：
2015-04
影响因子：
5.4
通讯作者：
Peng Y
中科院分区：
文献类型：
--
作者：
Yin J;Wang Y;Gu L;Fan N;Ma Y;Peng Y
肥胖引起的内质网应激和炎症导致脂肪细胞功能紊乱，胰岛素通路受损。近年来的研究表明，了解自噬的生理作用具有重要意义。本研究采用体外模型，将3T3-L1脂肪细胞预加载棕榈酸酯（PA），生成人工增厚的成熟脂肪细胞。western blot分析和荧光显微镜显示，PA诱导自噬通量增加，微管相关蛋白1轻链3 (LC3)-II形成，透射电镜（TEM）证实了这一点。通过透射电镜（TEM）和western blot分析，我们观察到内质网应激响应增加，内质网应激标记物BiP、激活转录因子4 （ATF4）和C/EBP同源蛋白（CHOP）水平升高，真核翻译起始因子2α和C - jun n -末端激酶（JNK）磷酸化。值得注意的是，我们观察到pa诱导的内质网应激发生在自噬激活之前。我们证实，自噬是在JNK依赖性内质网应激下诱导的，因为内质网应激抑制剂4-苯基丁酸酯（4-PBA）和JNK抑制剂SP600125抑制了自噬。在使用氯喹（CQ）抑制自噬后，我们观察到内质网应激加剧和细胞死亡水平增加。重要的是，为了确定自噬是否与炎症有关，使用了自噬抑制剂3-甲基腺嘌呤（3-MA）。自噬的抑制导致pa诱导的单核细胞趋化蛋白-1 （MCP-1）和白细胞介素-6 （IL-6）的表达进一步增加。同样，用SP600125治疗后也观察到这种增加。总之，我们的数据表明，PA引发内质网应激- jnk自噬轴，这对PA诱导的肥大脂肪细胞死亡和应激具有促生存作用。jnk依赖性的自噬激活可减少pa诱导的炎症。因此，刺激自噬可能成为一种减轻脂肪细胞功能障碍和炎症的方法。
Endoplasmic reticulum (ER) stress and inflammation induced by obesity lead to adipocyte dysfunction, with the impairment of the insulin pathway. Recent studies have indicated that understanding the physiological role of autophagy is of great significance. In the present study, an in vitro model was used in which 3T3-L1 adipocytes were pre-loaded with palmitate (PA) to generate artificially hypertrophied mature adipocytes. PA induced an autophagic flux, determined by an increased microtubule-associated protein 1 light chain 3 (LC3)-II formation, as shown by western blot analysis and fluorescence microscopy, and was confirmed using transmission electron microscopy (TEM). Using TEM and western blot analysis, we observed increased ER stress in response to PA, as indicated by the increased levels of the ER stress markers, BiP, activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and the phosphoralytion of eukaryotic translation initiation factor 2α and c-Jun N-terminal kinase (JNK). Of note, we observed that the PA-induced ER stress occurred prior to the activation of autophagy. We confirmed that autophagy was induced in response to JNK-dependent ER stress, as autophagy was suppressed by treatment with the ER stress inhibitor, 4-phenyl butyrate (4-PBA), and the JNK inhibitor, SP600125. Upon the inhibition of autophagy using chloroquine (CQ), we observed exacerbated ER stress and an increased level of cell death. Importantly, to determine whether autophagy is linked to inflammation, the autophagy inhibitor, 3-methyladenine (3-MA) was used. The inhibition of autophagy led to a further increase in the PA-induced expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). Consistently, such an increase was also observed following treatment with SP600125. In conclusion, our data indicate that PA elicits a ER stress-JNK-autophagy axis, and that this confers a pro-survival effect against PA-induced cell death and stress in hypertrophied adipocytes. The JNK-dependent activation of autophagy diminishes PA-induced inflammation. Therefore, the stimulation of autophagy may become a method with which to attenuate adipocyte dysfunction and inflammation.
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影响因子：
29
作者：
Martinez J;Verbist K;Wang R;Green DR
通讯作者：
Green DR
白藜芦醇通过 cAMP 信号通路诱导自噬减轻血管内皮炎症
影响因子：
13.3
作者：
Chen, Ming-liang;Yi, Long;Mi, Man-tian
通讯作者：
Mi, Man-tian
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：
30.8
作者：
Ravikumar, B;Vacher, C;Rubinsztein, DC
通讯作者：
Rubinsztein, DC