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Exp Clin Endocrinol Diabetes 2021; 129(09): 625-633
DOI: 10.1055/a-1240-4936
Article

Glucagon Like Peptide-1 Receptor Agonists Alter Pancreatic and Hepatic Histology and Regulation of Endoplasmic Reticulum Stress in High-fat Diet Mouse Model

Authors

  • Taiyong Fang‡

    Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China

  • Siying Huang‡

    Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China

  • Yongpeng Chen

    Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China

  • Zongchi Chen

    Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China

  • Jiangmu Chen

    Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China

  • Weitao Hu

    Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China

Funding This study was supported by Quanzhou Science and Technology Bureau, Fujian Province, China (Grant No. 2018N017S).
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Abstract

Background Obesity is a major health problem worldwide, and non-alcoholic fatty pancreas disease (NAFPD) and non-alcoholic fatty liver disease (NAFLD) are obesity-associated complications. Liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, has been approved for treatment of obesity. We aimed to evaluate the therapeutic effects of liraglutide on the complications through its regulation of endoplasmic reticulum (ER) stress.

Methods A high-fat diet mouse model was established in C57BL/6J mice. Two groups of mice were fed a high-fat diet with 60% fat for 16 weeks and control mice were fed standard chow. A four-week 0.6 mg/kg/day liraglutide treatment was started in one high-fat diet group after 12 weeks of the high-fat diet. After sacrificing the mice, pancreatic and hepatic tissues were prepared for western blot and immunohistochemistry for ER stress proteins, including activating transcription factor 4 (ATF4), caspase 12, C/EBP homologous protein (CHOP) eukaryotic initiation factor 2 α (eIF2α), glucose regulated protein (GRP) 78 and protein kinase RNA-like endoplasmic reticulum kinase (PERK).

Results Liraglutide significantly decreased body weight gained by mice consuming a high-fat diet (27.6 g vs. 34.5 g, P<0.001), and levels of all ER proteins increased significantly in both the pancreas and liver (all P<0.05). Expression of most ER stress proteins in pancreatic tissue correlated with disease scores of NAFLD (all P<0.05). However, no significant differences were found in pancreatic ATF 4 expression between mice without NAFLD, and those with early non-alcoholic steatohepatitis (NASH) and fibrotic NASH (P=0.122).

Conclusion Liraglutide may reduce the severity of NAFPD and NAFLD through regulating the ER stress pathway and downstream apoptosis signaling.

Key words

non-alcoholic fatty pancreas disease - non-alcoholic fatty liver disease - endoplasmic reticulum stress - glucagon-like peptide-1 receptor agonist


Publication History

Received: 13 March 2020
Received: 04 August 2020

Accepted: 10 August 2020

Article published online:
22 September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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