PEX-168 Improves Insulin Resistance, Inflammatory Response and Adipokines in Simple Obese Mice and Explore the Mechanism

Abstract Background: Polyethylene glycxol losenatide（PEX-168）is a new anti-diabetic drug and there are no reports on its weight loss effects，so we designed this trial to investigate the effect of PEX-168 on simple obese mice. Methods: Thirty healthy C57BL/6 male mice were randomly selected and divided into a blank control group (NC, n=6) and an obesity model group (n=24), the high-fat diet-induced simple obesity mice were divided into a model control group (HF) and three different doses of PEX-168 intervention groups of low (LD), medium (MD) and high (HD) (the doses of PEX-168 were 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg), 6 animals in each group. The intervention groups were injected with different doses of PEX-168 intraperitoneally once a week for 12 weeks, and fasting blood glucose (FBG), body weight and food intake were measured from 1 to 12 weeks after the injection, and the activity of mice was observed, and serum insulin (INS), CRP, chemerin and omentin levels were measured after 12 weeks. Results: Compared with the HF group, the low dose of PEX-168 could reduce the body weight of mice in a short period of time (8 weeks), and the mice in the LD and HD groups had a significant decrease in body weight (P < 0.05)；the low dose of PEX-168 could effectively improve the blood glucose and Homa-IR of mice (FBG P < 0.05 INS, IR P < 0.001), but there was no statistical difference between different doses (P > 0.05)；CRP levels in HD and LD groups were significantly improved(P < 0.05)，the levels of serum chemerin and omentin in intervention groups were significantly improved (P < 0.01), but there was no statistical difference between the different doses (P > 0.05). Conclusion: Continuous 12W administration of PEX-168 significantly reduced body weight in simple obese mice, thereby improving inflammatory status, improving insulin resistance, reducing serum chemerin level and increasing serum omentin level, inhibiting the development of diabetes. PEX-168 may regulate the expression of chemerin and omentin mainly through its hypoglycemic effect.