Understanding the Mechanisms of Glucagon-like Peptide-1 (GLP-1) and its Influence on Energy Expenditure
Introduction
Glucagon-like peptide-1 (GLP-1) is a hormone that plays a crucial role in regulating appetite and energy homeostasis. Obesity results from an imbalance between energy intake and energy expenditure (EE), and GLP-1 receptor (GLP-1R) agonists have been shown to reduce weight through appetite suppression. However, the influence of GLP-1 on energy expenditure has been poorly understood and remains a subject of debate. This article reviews the current understanding of how GLP-1 influences energy expenditure and its potential therapeutic applications.GLP-1 and Energy Expenditure: A Complex Relationship
Central vs. Peripheral Actions of GLP-1
Central GLP-1R activation has been shown to increase energy expenditure by stimulating brown adipose tissue thermogenesis. However, peripheral GLP-1R activation in the liver has been found to reduce energy expenditure by promoting glycogen synthesis. The pendulum of GLP-1's influence on energy expenditure may thus swing both ways, depending on the tissue and pathway involved. Clinical trials have investigated the effect of GLP-1 agonists on energy expenditure in adults. While some studies have shown a significant increase in energy expenditure, others have reported no significant change. The inconsistency may be due to differences in study design, population characteristics, and the specific GLP-1 agonist used. A recent study found that GLP-1 levels were inversely correlated with resting energy expenditure (REE) and respiratory quotient (RQ) in overweight and obese adults.GLP-1 and Substrate Oxidation
Implications for Weight Loss and Metabolic Health
GLP-1 agonists, including GLP-1 itself and its agonists, have been shown to be effective for promoting weight loss and improving glycemic control. The influence of GLP-1 on energy expenditure is a critical factor in its therapeutic potential. Although GLP-1 agonists primarily reduce weight through appetite suppression, their potential to influence energy expenditure could be further explored to enhance their efficacy. As an investigational triple-hormone receptor agonist (GLP-1+ GIP + glucagon), retatrutide may offer a new perspective on increasing energy expenditure as it targets all three receptors simultaneously.Conclusion
