کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11023062 | 1701347 | 2018 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces hepatic steatosis and endoplasmic reticulum stress by inducing nuclear factor erythroid-derived 2-related factor 2 nuclear translocation
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کلمات کلیدی
SCD1GLP-1UPRIRE1eIF2αATF6Heme oxygenase-1NQO-1Cpt1αSREBP1cstearoyl-CoA desaturase-1FABP1XBP-1DGAT1Inositol-requiring enzyme-1NAFLDGPAT1Nrf2FASHO-1HFDEx-4PPARBiP - BIPC/EBP homologous protein - C / EBP پروتئین همولوگsmall interfering RNAs - RNA های تداخل کوچکsiRNA - siRNAnonalcoholic steatohepatitis - استاتو هپاتیت غیر الکلیEndoplasmic reticulum stress - استرس شبکه آندوپلاسمیfatty acid synthase - اسید چرب سنتازexendin-4 - اگزنتین 4Nonalcoholic fatty liver disease - بیماری کبدی چربی غیر الکلیCHOP - تکه کردنminimum essential medium - حداقل حداقل مورد نیازhigh-fat diet - رژیم غذایی با چربی بالاnormal chow diet - رژیم غذایی معمول چوendoplasmic reticulum - شبکه آندوپلاسمی eukaryotic translation initiation factor 2α - عامل آغازگر ترجمه یوکاریوتی 2αMEM - مامانNash - نوشUnfolded protein response - پاسخ پروتئین آشکارBinding immunoglobulin Protein - پروتئین ایمونوگلوبولین BindingSterol regulatory element binding protein-1c - پروتئین متصل کننده پروتئین Sterlol-1cprotein kinase RNA-like ER kinase - پروتئین کیناز RNA مانند ER kinasePERK - پرکglucagon-like peptide-1 - پپتید 1-گلوکاگون-مانندperoxisome proliferator-activated receptor - گیرنده فعال فعال پروکسیوم
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Activation of endoplasmic reticulum (ER) stress is involved in the development of nonalcoholic fatty liver disease. Glucagon-like peptide-1 (GLP-1) has been reported to reduce hepatic steatosis, but the underlying mechanism has not been fully elucidated. Here, we investigated whether exendin-4 (EX-4), a GLP-1 receptor analogue, improves hepatic steatosis through ER stress reduction. Furthermore, we explored which ER stress pathway is involved in this process, with a focus on the protein kinase RNA-like ER kinase (PERK)-nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway. EX-4 treatment reduced hepatic lipid accumulation by suppressing the expression of lipogenic genes and restoring the expression of β-oxidation genes in palmitate-treated HepG2 cells and high fat diet (HFD)-fed mice. In addition, EX-4 treatment suppressed hepatic ER stress activation in HFD-fed mice and tunicamycin-treated mice. In particular, EX-4 treatment restored HFD- and tunicamycin-induced Nrf2 nuclear translocation to control levels. Inhibition of Nrf2 by siRNA enhanced phosphorylation of PERK and eukaryotic translation initiation factor 2α (eIF2α), as well as other substrates of the PERK pathway. Nrf2 knockdown also inhibited the protective effects of EX-4 against lipid accumulation, ER stress activation, and cell death in palmitate-treated HepG2 cells. EX-4 treatment prevents hepatic steatosis and improves cell survival by regulating hepatic lipid metabolism and reducing ER stress activation, and Nrf2 plays an essential role in the protective effect of GLP-1 on hepatic steatosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 360, 1 December 2018, Pages 18-29
Journal: Toxicology and Applied Pharmacology - Volume 360, 1 December 2018, Pages 18-29
نویسندگان
Jin Yoo, In-Jin Cho, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung, You-Cheol Hwang,