Abstract
BackgroundPolyethylene 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.MethodsThirty 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.ResultsCompared 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).ConclusionsPEX-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.
Highlights
The incidence rate of obesity has doubled in recent decades, which has caused health challenges among the world population [1]
General conditions All three groups of mice in the intervention group had a significant decrease in activity and water intake after being injected with Polyethylene glycol loxenatide (PEX-168) during the first two weeks, especially in the three days after the injection
Body weight and food intake In the present study, low doses of PEX-168 inhibited the progression of obesity in the short term, and medium to high concentrations of PEX-168 inhibited the Insulin resistance In this study, the hypoglycaemic effect of PEX-168 on simple obese mice manifested at low doses, and all three doses of PEX-168 inhibited the development of prediabetes and improved insulin resistance in nondiabetic
Summary
The incidence rate of obesity has doubled in recent decades, which has caused health challenges among the world population [1]. Obesity is a risk factor of cardiovascular disease and type 2 diabetes mellitus [2], and increases the financial burden of medical care [3]. New treatment options are of great significance for overweight and obese patients without type 2 diabetes to better manage their weight, and prevent or improve insulin resistance and inflammation, thereby reducing the risk of diabetes and improving their quality of life [7]. Polyethylene glycol loxenatide (PEX-168) is a new antidiabetic drug; as such, there are not yet any reports on its weight loss effect. This trial was designed to investigate the effect of PEX-168 on simple obese mice
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