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

中文翻译：

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胰高血糖素样肽-1 受体激动剂改变高脂饮食小鼠模型中的胰腺和肝脏组织学和内质网应激的调节。

背景肥胖是世界范围内的主要健康问题，非酒精性脂肪性胰腺疾病（NAFPD）和非酒精性脂肪肝（NAFLD）是肥胖相关的并发症。利拉鲁肽是一种胰高血糖素样肽-1 (GLP-1) 激动剂，已被批准用于治疗肥胖症。我们旨在通过调节内质网 (ER) 应激来评估利拉鲁肽对并发症的治疗效果。方法在C57BL/6J小鼠中建立高脂饮食小鼠模型。两组小鼠喂食含 60% 脂肪的高脂肪饮食 16 周，对照组小鼠喂食标准食物。在高脂饮食 12 周后，在一个高脂饮食组中开始为期 4 周的 0.6 mg/kg/天利拉鲁肽治疗。牺牲老鼠后，胰腺和肝组织被制备用于蛋白质印迹和免疫组织化学的 ER 应激蛋白，包括激活转录因子 4 (ATF4)、半胱天冬酶 12、C/EBP 同源蛋白 (CHOP) 真核起始因子 2 α (eIF2α)、葡萄糖调节蛋白 (GRP) ) 78 和蛋白激酶 RNA 样内质网激酶 (PERK)。结果 利拉鲁肽显着降低高脂饮食小鼠体重增加（27.6 g vs. 34.5 g，P<0.001），胰腺和肝脏中所有​​ER蛋白水平显着升高（均P<0.05）。胰腺组织中大部分ER应激蛋白的表达与NAFLD疾病评分相关（均P<0.05）。然而，没有发现 NAFLD 小鼠的胰腺 ATF 4 表达没有显着差异，以及患有早期非酒精性脂肪性肝炎 (NASH) 和纤维化 NASH (P=0.122) 的患者。结论 利拉鲁肽降低 NAFPD 的严重程度，NAFLD 可能通过调节 ER 应激通路和下游细胞凋亡信号通路。