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EGLP-1 lowers body weight better than exendin-4 by reducing food intake and increasing basal energy expenditure in diet-induced obese mice
Experimental Cell Research ( IF 3.7 ) Pub Date : 2020-12-25 , DOI: 10.1016/j.yexcr.2020.112454
Huashan Gao , Qian Zhao , Kaiying Li , Fujian Qin , Xin Yin , Zhou Lu , Ziwei Song , You Wu , Yumeng Shen , Yi Pan , Liang Jin , Yanfeng zhang

It is well known that GLP-1 activates GLP-1R to reduce body weight by inhibiting eating. GLP-1 is cleaved by the neutral endopeptidase (NEP) 24.11 into a pentapeptide GLP-1 (32–36) amide, which increases basal energy expenditure and inhibits weight gain in obese mice. It is well known that GLP-1 analogs can reduce weight by suppressing eating. However, there are few reports of reducing weight through the dual effects of inhibiting eating and increasing basic energy. Here, we report the peptide EGLP-1, a GLP-1 analogue, which can reduce food intake and increase basal energy expenditure. In C2C12 myotubes, EGLP-1 can increase both phosphorylation of acetyl CoA carboxylase (ACC) and the ratio between phosphorylation of ACC and the total expression of ACC (pACC/ACC). In diet-induced obese mice, EGLP-1 is more effective than exendin-4 in reducing body weight, reducing fat mass and improving hepatic steatosis. At the same time, EGLP-1 can improve hyperglycemia, reduce food intake, and improve insulin resistance, just like exendin-4. In addition, EGLP-1, not exendin-4, can improve physiological parameters associated with lipid metabolism and increase oxygen consumption by increasing uncoupling proteins 3 (UCP3) expression and pACC/ACC ratio in skeletal muscle. Taken together, this data showed that EGLP-1 is able to reduce body weight by reducing food intake and increasing basal energy expenditure, suggesting it may be more effective in treating diabetic and non-diabetic overweight or obese people than pure GLP-1R agonist exendin-4.



中文翻译:

EGLP-1通过减少饮食摄入和增加饮食诱发的肥胖小鼠的基础能量消耗而比exendin-4更好地减轻了体重

众所周知,GLP-1通过抑制进食来激活GLP-1R以减轻体重。GLP-1被中性内肽酶(NEP)24.11裂解为五肽GLP-1(32-36)酰胺,这增加了基础能量消耗并抑制了肥胖小鼠的体重增加。众所周知,GLP-1类似物可以通过抑制进食来减轻体重。然而,很少有报道通过抑制进食和增加基本能量的双重作用来减轻体重。在这里,我们报告了EGLP-1肽(一种GLP-1类似物),它可以减少食物摄入并增加基础能量消耗。在C2C12肌管中,EGLP-1既可以增加乙酰辅酶A羧化酶(ACC)的磷酸化,又可以增加ACC磷酸化与ACC总表达的比率(pACC / ACC)。在饮食诱发的肥胖小鼠中,EGLP-1在减轻体重,减少脂肪量和改善肝脂肪变性方面比exendin-4更有效。同时,就像exendin-4一样,EGLP-1可以改善高血糖,减少食物摄入并改善胰岛素抵抗。另外,EGLP-1(不是exendin-4)可以通过增加骨骼肌中的解偶联蛋白3(UCP3)表达和pACC / ACC比率来改善与脂质代谢相关的生理参数,并增加耗氧量。总体而言,该数据表明EGLP-1能够通过减少食物摄入量和增加基础能量消耗来减轻体重,这表明它比纯GLP-1R激动剂exendin更有效地治疗糖尿病和非糖尿病超重或肥胖的人-4。就像exendin-4一样,减少食物摄入并改善胰岛素抵抗。另外,EGLP-1(不是exendin-4)可以通过增加骨骼肌中的解偶联蛋白3(UCP3)表达和pACC / ACC比率来改善与脂质代谢相关的生理参数,并增加耗氧量。总体而言,该数据表明EGLP-1能够通过减少食物摄入量和增加基础能量消耗来减轻体重,这表明它比纯GLP-1R激动剂exendin更有效地治疗糖尿病和非糖尿病超重或肥胖的人-4。就像exendin-4一样,减少食物摄入并改善胰岛素抵抗。另外,EGLP-1(不是exendin-4)可以通过增加骨骼肌中的解偶联蛋白3(UCP3)表达和pACC / ACC比率来改善与脂质代谢相关的生理参数,并增加耗氧量。总体而言,该数据表明EGLP-1能够通过减少食物摄入量和增加基础能量消耗来减轻体重,这表明它比纯GLP-1R激动剂exendin更有效地治疗糖尿病和非糖尿病超重或肥胖的人-4。可以通过增加骨骼肌中的解偶联蛋白3(UCP3)表达和pACC / ACC比来改善与脂质代谢相关的生理参数并增加耗氧量。总体而言,该数据表明EGLP-1能够通过减少食物摄入量和增加基础能量消耗来减轻体重,这表明它比纯GLP-1R激动剂exendin更有效地治疗糖尿病和非糖尿病超重或肥胖的人-4。可以通过增加骨骼肌中的解偶联蛋白3(UCP3)表达和pACC / ACC比来改善与脂质代谢相关的生理参数并增加耗氧量。总体而言,该数据表明EGLP-1能够通过减少食物摄入量和增加基础能量消耗来减轻体重,这表明它比纯GLP-1R激动剂exendin更有效地治疗糖尿病和非糖尿病超重或肥胖的人-4。

更新日期:2020-12-29
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