The Weight-Loss Breakthrough: How Liraglutide Targets Your Brain to Help You Shed Pounds Fast!
liraglutide help weight loss
New Study Explains How Liraglutide Helps with Weight Loss
A recent study has spotlighted the pivotal function of lateral septum neurons in the effectiveness of the anti-obesity drug liraglutide, revealing new dimensions for potential obesity treatments.
Under the leadership of Prof. Yingjie Zhu at the Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), researchers have identified the essential role played by lateral septum (LS) neurons in moderating the appetite-suppressing and weight-reducing impacts of liraglutide in murine models.
The findings were published in the Journal of Clinical Investigation.
Obesity has escalated to one of the top ten chronic conditions globally, contributing to numerous health complications and intensifying the burden on healthcare systems.
Anti-obesity drugs have demonstrated superior efficacy compared to lifestyle interventions and dietary changes, with fewer risks and complications than surgical options. Since 2014, GLP-1 receptor agonists have emerged as a transformative category of medications, significantly outperforming other weight-loss treatments in terms of both efficacy and safety.
These drugs, particularly in diabetes and obesity management, are on the trajectory of becoming the next wave of “blockbuster” pharmaceuticals.
liraglutide help weight loss: Mechanisms of GLP-1 and Liraglutide
Glucagon-like peptide-1 (GLP-1) is an incretin hormone encoded by the proglucagon gene (GCG), predominantly secreted by intestinal L cells and certain neurons in the brainstem. Its effects are mediated through the GLP-1 receptor (GLP-1R), a class B G protein-coupled receptor expressed widely throughout both the peripheral and central nervous systems.
Liraglutide, a short-acting GLP-1R agonist, curbs appetite and delays gastric emptying, establishing it as the first GLP-1-based anti-obesity medication available on the market.
Despite the broad presence of GLP-1Rs in the brain, the specific neural pathways through which these agonists regulate food consumption and body weight have remained elusive.
This research revealed that GLP-1 receptors (GLP-1Rs) are abundantly expressed in the dorsal LS. Liraglutide significantly activated these GLP-1R-positive (LSGLP-1R) neurons.
Moreover, knocking down GLP-1Rs in the LS diminished liraglutide’s ability to suppress appetite and reduce weight, whereas targeted knockdown in hypothalamic regions like the paraventricular nucleus (PVN) and arcuate nucleus (Arc) did not replicate this effect. This underscores the crucial role that GLP-1Rs in the LS play in liraglutide’s anorectic action.
Neural Activity and Behavioral Implications
In addition, the researchers examined the intrinsic activity of LSGLP-1R neurons during natural feeding by employing fiber photometry in freely moving mice.
They noted a marked decrease in Ca2+ signals when food consumption began, which persisted throughout the feeding period and normalized after the cessation of eating. Activation of these neurons suppressed feeding and promoted weight reduction, mirroring liraglutide’s effects.
Conversely, deactivation of these neurons significantly impaired liraglutide’s efficacy in suppressing appetite and reducing weight.
This investigation offers profound insights into the neural mechanisms that govern feeding behavior, laying the groundwork for innovative treatments for eating disorders and obesity, and broadening the understanding of the GLP-1 signaling pathway.
Reference
“GLP-1R–positive neurons in the lateral septum mediate the anorectic and weight-lowering effects of liraglutide in mice” by Zijun Chen, Xiaofei Deng, Cuijie Shi, Haiyang Jing, Yu Tian, Jiafeng Zhong, Gaowei Chen, Yunlong Xu, Yixiao Luo, and Yingjie Zhu, 3 September 2024, The Journal of Clinical Investigation. DOI: 10.1172/JCI178239.
