Oleic acid acutely impairs glucose homeostasis in standard chow diet but not high-fructose, high-fat diet-fed mice by acting on free fatty acid receptor 1

Abstract This study aimed to investigate the acute effects of oleic acid (OA) on glucose homeostasis in mice fed a standard chow diet (SCD) and a high-fructose, high-fat diet (HFrHFD); moreover, the role of free fatty acid receptor 1 (FFAR1) was evaluated. The mice in the two groups were further divided into three subgroups as follows: control, OA (40 mg/kg), and OA + GW1100 (0.4 mg/kg, selective FFAR1 blocker). After a 16-week feeding period, the mice received the drugs via intraperitoneal (i.p.) injection followed by an i.p. glucose tolerance test (IPGTT) 30 min later. After 3 days, the mice received the same drugs to examine the effects of the drugs on the hepatic levels of phosphatidylinositol-4,5-bisphosphate (PIP2) and diacylglycerol (DAG). OA in the SCD-fed mice significantly increased the blood glucose level (48%, P摘要 本研究旨在探究油酸（oleic acid, OA）对饲喂标准饲料饮食（standard chow diet, SCD）与高果糖高脂饮食（high-fructose, high-fat diet, HFrHFD）小鼠葡萄糖稳态的急性影响，同时评估游离脂肪酸受体1（free fatty acid receptor 1, FFAR1）的作用。将两组饲喂不同饮食的小鼠进一步划分为三个亚组：对照组、油酸给药组（40 mg/kg）以及油酸+GW1100给药组（0.4 mg/kg，选择性FFAR1阻断剂）。在16周饲养周期结束后，通过腹腔（intraperitoneal, i.p.）注射方式对小鼠给药，并于给药30分钟后开展腹腔葡萄糖耐量试验（intraperitoneal glucose tolerance test, IPGTT）。3日后，小鼠再次接受相同给药处理，以检测药物对肝脏中磷脂酰肌醇-4,5-二磷酸（phosphatidylinositol-4,5-bisphosphate, PIP2）与二酰甘油（diacylglycerol, DAG）水平的影响。饲喂标准饲料饮食的小鼠经油酸处理后，血糖水平显著升高（增幅达48%，P