1. Glucagon Like Peptide-1 Receptor Agonists Alter Pancreatic and Hepatic Histology and Regulation of Endoplasmic Reticulum Stress in High-fat Diet Mouse Model.
- Author
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Fang T, Huang S, Chen Y, Chen Z, Chen J, and Hu W
- Subjects
- Animals, Diet, High-Fat, Disease Models, Animal, Hypoglycemic Agents administration & dosage, Liraglutide administration & dosage, Male, Mice, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease etiology, Obesity complications, Pancreatic Diseases etiology, Endoplasmic Reticulum Stress drug effects, Hypoglycemic Agents pharmacology, Liraglutide pharmacology, Non-alcoholic Fatty Liver Disease drug therapy, Obesity drug therapy, Pancreatic Diseases drug therapy, Glucagon-Like Peptide-1 Receptor Agonists
- 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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)
- Published
- 2021
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