title: High-density lipoprotein inhibits ox-LDL-induced adipokine secretion by upregulating SR-BI expression and suppressing ER Stress pathway.
abstract: 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.
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, TaiShan Medical University, Taian, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Song
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, TaiShan Medical University, Taian, China.|Institute of Nursing, TaiShan Medical University, Taian, China.|Central Hospital of Taian City, Taian, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Central Hospital of Taian City, Taian, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, TaiShan Medical University, Taian, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, TaiShan Medical University, Taian, China.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, TaiShan Medical University, Taian, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Jiao
authors.affiliation: Maternal and child health hospital of Daiyue District, Taian, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Wang
authors.affiliation: Maternal and child health hospital of Daiyue District, Taian, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Song
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, TaiShan Medical University, Taian, China.
authors.forename: You
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease and Hebei Key Laboratory of Vascular Homeostasis, Shijiazhuang, 050000, China.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Nursing, TaiShan Medical University, Taian, China.
authors.forename: Huaxia
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, TaiShan Medical University, Taian, China.
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
mesh_terms: D041721:3T3-L1 Cells; D051702:Activating Transcription Factor 6 / Q000378:metabolism; D054392:Adipokines / Q000097:blood / Q000378:metabolism*; D000818:Animals; D018955:CD36 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D051379:Mice; D054409:Nicotinamide Phosphoribosyltransferase / Q000032:analysis / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010654:Phenylbutyrates / Q000494:pharmacology; D034622:RNA Interference; D052243:Resistin / Q000032:analysis / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D054392:Adipokines; D018955:CD36 Antigens; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D054409:Nicotinamide Phosphoribosyltransferase; D010654:Phenylbutyrates; D052243:Resistin; D051742:Transcription Factor CHOP; D014415:Tunicamycin; D019892:eIF-2 Kinase; C497112:Atf6 protein, mouse; C497250:Ddit3 protein, mouse; C099252:oxidized low density lipoprotein; C075773:4-phenylbutyric acid