Hormonal
The dual GLP-1/glucagon receptor agonist G49 induces rapid weight loss and metabolic rewiring in diet-induced obese mice by triggering inter-organ crosstalk, specifically white adipose tissue lipolysis, liver ketogenesis/FGF21 release, and subsequent brown adipose tissue activation.
This research suggests that combining GLP-1 and Glucagon receptor activation (like the drug G49) is more effective for weight loss and metabolic health than targeting GLP-1 alone. It works by forcing the body to burn fat (lipolysis) and activate brown fat, mimicking the effects of bariatric surgery. While promising in mice, human clinical data is not yet provided in this paper.
Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist, triggers an inter-organ cross-talk between adipose tissue, pancreas, and liver which is initiated by a rapid release of free fatty acids (FFAs) by white adipose tissue (WAT) in a GCGR-dependent manner. This interactome leads to elevations in adiponectin and fibroblast growth factor 21 (FGF21), causing WAT beiging, brown adipose tissue (BAT) activation, increased energy expenditure (EE) and weight loss.
Why this rating
High-quality preclinical data (mice, human explants) but lacks human clinical trial results for efficacy.
Source
The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk
M. Pilar Valdecantos et al. · Nature Communications · 2024
DOI 10.1038/s41467-024-54080-w
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