- Ángela Martínez Valverde's team describes the mechanism of action of a pharmacological alternative to bariatric surgery
- The results, published in Nature Communications, could pave the way for new therapies for obesity and type 2 diabetes
The research group led by Dr. Ángela Martínez Valverde at the Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), CSIC-UAM, has published in Nature Communications the mechanism of action of a compound called G49, which promotes weight loss in obese mice and induces metabolic changes similar to those observed in humans after bariatric surgery. This significant study suggests that G49 could represent a non-surgical alternative for individuals suffering from morbid obesity.
"Although bariatric surgery is effective for treating and inducing remission of obesity and type 2 diabetes, new pharmacological treatments are needed to induce similar metabolic adaptations without the risks and complications associated with surgical procedures," explain M. Pilar Valdecantos and Ángela Martínez Valverde, the lead researchers of this study at IIBM and members of the Diabetes and Associated Metabolic Diseases area of CIBER (CIBERDEM).
This discovery falls within the context of new therapies for obesity treatment based on incretins—hormones released in response to nutrient intake that also stimulate insulin secretion from the pancreas. The G49 peptide, a dual agonist of glucagon-like peptide-1 (GLP-1) receptors and glucagon receptors, has been identified as a potential pharmacological alternative that mimics the hormonal and metabolic pathways of bariatric surgery. This study is the first to describe the mechanisms of action of such dual agonists.
The research demonstrated how the G49 peptide triggers an interaction between adipose tissue, the pancreas, and the liver, beginning with a rapid release of free fatty acids from white adipose tissue that depends on the glucagon receptor. "These interactions lead to an increase in adiponectin and fibroblast growth factor 21 (FGF21), promoting the browning of white adipose tissue and the activation of brown adipose tissue," the researchers add. These metabolic changes induced by G49 result in increased energy expenditure and weight loss. In the plasma of obese individuals who underwent Roux-en-Y gastric bypass surgery, an increase in oxyntomodulin was observed, along with metabolic adaptations similar to those induced in obese mice treated with the G49 peptide.
Several researchers from IIBM contributed to this study, in addition to the coordinators M. Pilar Valdecantos and Ángela Martínez Valverde. Other participants included Laura Ruiz, Patricia Rada, Irma García-Martínez, and Ana B. Hitos, as well as groups from various Centros de Investigación Biomédica en Red (CIBER), researchers from AstraZeneca, and the Universidad de Graz.
The article can be read HERE