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PEX-168 改善单纯性肥胖小鼠的胰岛素抵抗、炎症反应和脂肪因子:机制探讨。

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

机构信息

College of Nursing, Yangzhou University, Yangzhou, China.

Northern Jiangsu People's Hospital, Yangzhou, China.

出版信息

BMC Endocr Disord. 2021 Dec 20;21(1):245. doi: 10.1186/s12902-021-00908-1.

DOI:10.1186/s12902-021-00908-1
PMID:34923973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8686575/
Abstract

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.

摘要

背景

聚乙二醇洛塞那肽(PEX-168)是一种新型的抗糖尿病药物;因此,目前尚无关于其减肥效果的报告。因此,本试验旨在研究 PEX-168 对单纯肥胖小鼠的影响。

方法

随机选取 30 只健康雄性 C57BL/6 小鼠,分为对照组(NC)和肥胖模型组。高脂饮食诱导的单纯肥胖小鼠分为模型对照组(HF)和 3 个干预组。干预组每周腹腔注射不同剂量的 PEX-168 一次,共 12 周(低(LD)、中(MD)和高(HD)剂量)。从 PEX-168 注射后第 1 周到第 12 周,测量空腹血糖(FBG)、体重和食物摄入量。注射后 12 周测量血清胰岛素(INS)、C 反应蛋白(CRP)、趋化素和网膜素水平。

结果

与 HF 组相比,低剂量 PEX-168 可在短时间内(8 周)降低小鼠体重,MD 和 HD 组小鼠体重明显下降(P < 0.05)。低剂量 PEX-168 能有效改善小鼠血糖和胰岛素抵抗稳态模型评估(Homa-IR)(FBG P < 0.05,INS,Homa-IR P < 0.001),但不同剂量之间无差异(P > 0.05)。MD 和 HD 组 CRP 水平明显改善(P < 0.05)。干预组血清趋化素和网膜素水平也明显改善(P < 0.01),但不同剂量之间无差异(P > 0.05)。

结论

PEX-168 可显著降低单纯肥胖小鼠体重,改善胰岛素抵抗。PEX-168 可能通过其降血糖作用调节趋化素和网膜素的表达,而 PEX-168 的减重作用不太可能是两者变化的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b512/8686575/31028c20a4ed/12902_2021_908_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b512/8686575/31028c20a4ed/12902_2021_908_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b512/8686575/31028c20a4ed/12902_2021_908_Fig1_HTML.jpg

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