GLP-1 receptor pathways show therapeutic potential for dual obesity and depression management

Obesity and depression are highly prevalent, often comorbid conditions that significantly impact global health. Current treatment strategies frequently address these disorders separately, despite their shared underlying biological pathways, including inflammation, oxidative stress, neurotransmitter imbalance, mitochondrial dysfunction, and HPA-axis dysregulation. This interconnectedness suggests a need for therapies that can target both conditions simultaneously, offering a more holistic approach to patient care and improving long-term outcomes.

This review systematically examined existing literature on Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) to elucidate their therapeutic potential for the dual management of obesity and depression. The authors focused on identifying shared biological pathways, including inflammation, oxidative stress, neurotransmitter imbalance, mitochondrial dysfunction, adipocytokine alterations, and gut-brain/HPA-axis dysregulation, that are mediated by GLP-1R signaling. The scope encompassed studies detailing GLP-1RAs' impact on metabolic parameters and neuroprotective effects.

The review synthesized evidence demonstrating that GLP-1RAs influence multiple interconnected pathways relevant to both obesity and depression. They were found to impact glycemic levels, promote weight reduction, and improve insulin sensitivity, alongside modulating appetite and satiety control. > Crucially, the analysis highlighted significant neuroprotective effects, including the modulation of dopaminergic pathways, enhanced hippocampal neurogenesis, and reduction of neuroinflammation. These findings suggest that GLP-1R signaling pathways offer a common therapeutic target, addressing the complex interplay of metabolic and neurological dysregulations underlying these comorbid conditions. The review specifically noted GLP-1RAs' ability to mitigate inflammation and oxidative stress, which are central to both conditions, and to positively influence neurotransmitter balance.