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.
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.
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。
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