PEX-168 improves insulin resistance, inflammatory response and adipokines in simple obese mice: a mechanistic exploration

BACKGROUND: Polyethylene glycol loxenatide (PEX-168) is a new antidiabetic drug; as such, there are not yet any reports on its weight loss effect. Therefore, this trial was designed to investigate the effect of PEX-168 on simple obese mice. METHODS: Thirty healthy male C57BL/6 mice were randomly selected and divided into a control group (NC) and an obesity model group. The high-fat diet-induced simple obesity mice were divided into a model control group (HF) and three intervention groups. The intervention groups were injected with different doses of PEX-168 intraperitoneally once a week for 12 weeks (low (LD), medium (MD) and high (HD)). Fasting blood glucose (FBG), body weight and food intake were measured from 1 to 12 weeks after PEX-168 injection. The serum insulin (INS), C-reactive protein (CRP), chemerin and omentin levels were measured after 12 weeks. RESULTS: Compared with the HF group, the low dose of PEX-168 reduced the body weight of the mice in a short period of time (8 weeks), and the mice in the MD and HD groups showed a significant decrease in body weight (P < 0.05). The low dose of PEX-168 could effectively improve the blood glucose and homeostasis model assessment of insulin resistance (Homa-IR) of the mice (FBG P < 0.05 INS, Homa-IR P < 0.001), but there was no significant difference between different doses (P > 0.05). CRP levels in the MD and HD groups were significantly improved (P < 0.05). The levels of serum chemerin and omentin in the intervention groups were also significantly improved (P < 0.01), but there was no significant difference between the different doses (P > 0.05). CONCLUSIONS: PEX-168 significantly reduced the body weight of simple obese mice and improved the insulin resistance. PEX-168 may regulate the expression of chemerin and omentin through its hypoglycaemic effect, and the weight-reducing effect of PEX-168 is unlikely to be the reason for the changes in both.