Effects of Chlorogenic Acid on Glucose Tolerance and Its Curve Characteristics in High-Fat Diet-Induced Obese Rats

Abstract

Abstract Objectives To observe the improvement effect and its mechanism of chlorogenic acid (CGA) on the glucose tolerance and its curve characteristics in high fat diet-induced obesity (DIO) rats. Methods Eight of 56 male SD rats were randomly selected as the normal diet group (CON), and the rest were fed with high-fat diet. After 4 weeks, 24 DIO rats were screened and then randomly divided into high fat diet group (HFD group), 50% CGA group and 98% CGA group. The CGA groups received intragastric administrations of 50% CGA and 98% CGA (80 mg/kg/d) once a day for 8 weeks, respectively, while the CON and HFD groups received a carrier solution PBS. Body weight was measured weekly and OGTT was performed every 4 weeks. Fasting insulin and insulin release were measured, HOMA-IR was calculated. Histopathological examination by hematoxylin and eosin staining method were evaluated in the pancreatic tissues. Non-targeted metabolomics analysis of rat serum was performed using UHPLC-Q-Orbitrap MS. Results Before the intervention of CGA, blood glucose levels at 120 min after glucose loading (P < 0.05) and AUC-G (P < 0.05) were higher in HFD group than in CON group, and time to glucose peak was delayed (P < 0.05). At the end of 8 weeks intervention, the HOMA-IR index, insulin levels at 0,30,60 and 120 min after glucose loading and AUC-I increased (P < 0.05), pancreatic islets obviously showed hypertrophy and hyperplasia (P < 0.05) in HFD group. Compared with the HFD group, OGTT-60 min, 120 min blood glucose and AUC-G (P < 0.05) were lower in 50% CGA and 98% CGA groups, HOMA-IR index and OGTT-0, 30, 120 min serum insulin level decreased (P < 0.05), time to glucose peak shifted to an earlier time point (P < 0.05), abnormal islet hyperplasia attenuated (P < 0.05). AUC-I decreased only in 98% CGA group (P < 0.05). Serum GM3 in HFD group increased, while Cer (AP t14:0/29:1) and LysoPC (18:2) decreased significantly. Compared with HFD group, serum Cer (AP t14:0/29:1) increased significantly in both CGA groups. Serum LysoPC (18:2) increased in 50% CGA group and GM3 decreased significantly in 98% CGA group. Conclusions Both of 50% and 98% CGA could improve the glucose tolerance and delay in glucose peak time through ADPNR1/2-mediated ceramidase activity pathway and improve insulin signaling pathway. Funding Sources The research was supported by the National Key Research and Development Program (NO. 2016YFD0400603).