Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet

Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After admin...

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Main Authors: Xiaoqing Ma, Wenhua Du, Shanshan Shao, Chunxiao Yu, Lingyan Zhou, Fei Jing
Format: Article
Language:English
Published: Hindawi Limited 2018-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2018/5045182
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spelling doaj-1658e9ab90b7439db973adc448716ed22020-11-25T00:59:01ZengHindawi LimitedBioMed Research International2314-61332314-61412018-01-01201810.1155/2018/50451825045182Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat DietXiaoqing Ma0Wenhua Du1Shanshan Shao2Chunxiao Yu3Lingyan Zhou4Fei Jing5Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, ChinaDepartment of Endocrinology, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan 250033, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, ChinaPurpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27%) and liver triglycerides (314.75%) compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.http://dx.doi.org/10.1155/2018/5045182
collection DOAJ
language English
format Article
sources DOAJ
author Xiaoqing Ma
Wenhua Du
Shanshan Shao
Chunxiao Yu
Lingyan Zhou
Fei Jing
spellingShingle Xiaoqing Ma
Wenhua Du
Shanshan Shao
Chunxiao Yu
Lingyan Zhou
Fei Jing
Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet
BioMed Research International
author_facet Xiaoqing Ma
Wenhua Du
Shanshan Shao
Chunxiao Yu
Lingyan Zhou
Fei Jing
author_sort Xiaoqing Ma
title Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet
title_short Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet
title_full Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet
title_fullStr Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet
title_full_unstemmed Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet
title_sort vildagliptin can alleviate endoplasmic reticulum stress in the liver induced by a high fat diet
publisher Hindawi Limited
series BioMed Research International
issn 2314-6133
2314-6141
publishDate 2018-01-01
description Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27%) and liver triglycerides (314.75%) compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.
url http://dx.doi.org/10.1155/2018/5045182
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