Exendin-4 Inhibits the Expression of SEPP1 and Fetuin-A via Improvement of Palmitic Acid-Induced Endoplasmic Reticulum Stress by AMPK.
10.3803/EnM.2015.30.2.177
- Author:
Jinmi LEE
1
;
Seok Woo HONG
;
Se Eun PARK
;
Eun Jung RHEE
;
Cheol Young PARK
;
Ki Won OH
;
Sung Woo PARK
;
Won Young LEE
Author Information
1. Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Exendin-4;
Palmitic acid;
Endoplasmic reticulum stress;
AMP-activated protein kinases;
Selenoprotein P;
Fetuin-A;
Hepatokine
- MeSH:
Activating Transcription Factor 6;
alpha-2-HS-Glycoprotein*;
AMP-Activated Protein Kinases*;
Blotting, Western;
Carcinoma, Hepatocellular;
Cell Line;
Endoplasmic Reticulum;
Endoplasmic Reticulum Stress*;
Fatty Liver;
Glucagon-Like Peptide 1;
Glycoproteins;
Hep G2 Cells;
Humans;
Insulin Resistance;
Palmitic Acid;
Phosphotransferases;
Polymerase Chain Reaction;
Reverse Transcription;
RNA, Small Interfering;
Selenoprotein P;
Transfection;
Tunicamycin;
Biomarkers;
Glucagon-Like Peptide-1 Receptor
- From:Endocrinology and Metabolism
2015;30(2):177-184
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is unknown. METHODS: The human hepatoma cell line HepG2 was treated with palmitic acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100 nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK) small interfering RNA (siRNA) was performed to establish the effect of exendin-4-mediated AMPK in the regulation of SEPP1 and fetuin-A expression. RESULTS: Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers including PKR-like ER kinase, inositol-requiring kinase 1alpha, activating transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4 also reduced the expression of SEPP1 and fetuin-A in cells treated with tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5-aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic SEPP1 and fetuin-A were negatively related by AMPK, which is the target of exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A expression in cells transfected with AMPK siRNA. CONCLUSION: These data suggest that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via improvement of PA-induced ER stress by AMPK.
