Song Guohua, Wu Xia, Zhang Pu, Yu Yang, Yang Mingfeng, Jiao Peng, Wang Ni, Song Haiming, Wu You, Zhang Xiangjian, Liu Huaxia, Qin Shucun
Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, TaiShan Medical University, Taian, China.
Institute of Nursing, TaiShan Medical University, Taian, China.
Sci Rep. 2016 Jul 29;6:30889. doi: 10.1038/srep30889.
Endoplasmic reticulum stress (ERS) in adipocytes can modulate adipokines secretion. The aim of this study was to explore the protective effect of high-density lipoprotein (HDL) on oxidized low-density lipoprotein (ox-LDL)-induced ERS-C/EBP homologous protein (CHOP) pathway-mediated adipokine secretion. Our results showed that serum adipokines, including visfatin, resistin and TNF-α, correlated inversely with serum HDL cholesterol level in patients with abdominal obesity. In vitro, like ERS inhibitor 4-phenylbutyric acid (PBA), HDL inhibited ox-LDL- or tunicamycin (TM, an ERS inducer)-induced increase in visfatin and resistin secretion. Moreover, HDL inhibited ox-LDL-induced free cholesterol (FC) accumulation in whole cell lysate and in the endoplasmic reticulum. Additionally, like PBA, HDL inhibited ox-LDL- or TM-induced activation of ERS response as assessed by the decreased phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α and reduced nuclear translocation of activating transcription factor 6 as well as the downregulation of Bip and CHOP. Furthermore, HDL increased scavenger receptor class B type I (SR-BI) expression and SR-BI siRNA treatment abolished the inhibitory effects of HDL on ox-LDL-induced FC accumulation and CHOP upregulation. These data indicate that HDL may suppress ox-LDL-induced FC accumulation in adipocytes through upregulation of SR-BI, subsequently preventing ox-LDL-induced ER stress-CHOP pathway-mediated adipocyte inflammation.
脂肪细胞中的内质网应激（ERS）可调节脂肪因子的分泌。本研究旨在探讨高密度脂蛋白（HDL）对氧化型低密度脂蛋白（ox-LDL）诱导的ERS- C/EBP同源蛋白（CHOP）途径介导的脂肪因子分泌的保护作用。我们的结果显示，在腹部肥胖患者中，包括内脂素、抵抗素和肿瘤坏死因子-α（TNF-α）在内的血清脂肪因子与血清HDL胆固醇水平呈负相关。在体外，与ERS抑制剂4-苯基丁酸（PBA）一样，HDL可抑制ox-LDL或衣霉素（TM，一种ERS诱导剂）诱导的内脂素和抵抗素分泌增加。此外，HDL可抑制ox-LDL诱导的全细胞裂解物和内质网中游离胆固醇（FC）的积累。另外，与PBA一样，HDL可抑制ox-LDL或TM诱导的ERS反应激活，这可通过蛋白激酶样内质网激酶和真核翻译起始因子2α磷酸化的降低、激活转录因子6核转位的减少以及结合免疫球蛋白蛋白（Bip）和CHOP的下调来评估。此外，HDL可增加I型清道夫受体B类（SR-BI）的表达，而SR-BI小干扰RNA（siRNA）处理可消除HDL对ox-LDL诱导的FC积累和CHOP上调的抑制作用。这些数据表明，HDL可能通过上调SR-BI来抑制ox-LDL诱导的脂肪细胞中FC的积累，从而预防ox-LDL诱导的内质网应激-CHOP途径介导的脂肪细胞炎症。
