Moderate preventative effect with intraperitoneal liraglutide injection in high-fat diet induced C57BL/6J obese mouse model

Abstract

BackgroundAlthough glucagon-like peptide-1 (GLP-1) based drugs including liraglutide have been among type 2 diabetes drugs for more than a decade, further studies with them in animal models may help to expand their future implications. ObjectiveHere we mainly assessed the potential preventative effect of liraglutide and the C-terminal fragment of GLP-1 (GLP-128-36) on obesity development in a high-fat-diet (HFD) induced obese mouse model. MethodsMale C57BL/6J mice were fed with HFD for 10 days (instead of 8 weeks or longer by other studies), followed by liraglutide, or GLP-128-36 administration 6 days per week for 5 weeks. In addition to daily body weight monitoring, oral glucose and intraperitoneal insulin tolerance tests were conducted. Plasma as well as hepatic triglyceride contents were also measured. ResultsIn comparison to PBS control, liraglutide but not GLP-128-36 administration, moderately attenuated HFD-induced body weight gain, accompanied by moderately improved glucose disposal and attenuated fasting blood glucose level. Liraglutide administration attenuated HFD induced hepatic and plasma triglyceride (TG) elevation, while GLP-128-36 administration reduced plasma but not hepatic TG level. In HFD fed mice, liraglutide treatment also improved insulin stimulated Akt (Ser473) phosphorylation in the liver. Notably, the daily body weight lowering effect of liraglutide was consistently decreased after the mice were rested for one day. ConclusionsWe conclude that preventative effect of liraglutide on obesity development is moderate in our experimental settings and such an effect was absent for GLP-128-36. Further investigations are needed for evaluating the weight management effect of both GLP-1-based and incretin-based drugs.