EGLP-1 lowers body weight better than exendin-4 by reducing food intake and increasing basal energy expenditure in diet-induced obese mice.

Abstract

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.

• Authors: Huashan Gao, Qian Zhao, Kaiying Li, Fujian Qin, Xin Yin, Zhou Lu, Ziwei Song, You Wu, Yumeng Shen, Yi Pan, Liang Jin, Yanfeng Zhang
• Journal: Experimental cell research (Exp Cell Res) Vol. 399 Issue 1 Pg. 112454 (02 01 2021) ISSN: 1090-2422 [Electronic] United States
• PMID: 33359447 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Obesity Agents
• Peptide Fragments
• Glucagon-Like Peptide 1
• Exenatide

Topics

• Animals
• Anti-Obesity Agents (pharmacology)
• Body Weight (drug effects)
• Cells, Cultured
• Diet, High-Fat
• Eating (drug effects, physiology)
• Energy Metabolism (drug effects)
• Exenatide (pharmacology, therapeutic use)
• Glucagon-Like Peptide 1 (chemistry, pharmacology, therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Obesity (drug therapy, etiology, metabolism)
• Peptide Fragments (pharmacology, therapeutic use)