Christine M. Kusminski, Ph.D., Associate Professor of Internal Medicine, and Xinxin Yu, M.D., Research Scientist, are exploring the effects of the glucose-dependent insulinotropic polypeptide receptor (GIPR) on fat cells as a potential therapy for obesity. Their study, published in Cell Metabolism, found that obese mice with genetically altered fat cells to produce more GIPR lost over a third of their body weight by burning energy more efficiently.
Key Findings:
- Significant Weight Loss: Obese mice lost approximately 35% of their body weight within two weeks after the extra GIPR in fat cells was activated.
- Resistance to Obesity: Normal-weight mice with activated extra GIPR in fat cells were resistant to developing obesity when fed a high-fat diet.
- Mechanism of Action: The increased GIPR led to heightened activity in sarco/endoplasmic reticulum calcium ATPase (SERCA) pathways, causing cells to burn extra ATP without transporting calcium, thus burning more energy and promoting weight loss.
- Metabolic Memory: Mice did not regain weight after the extra GIPR production was turned off, suggesting a 'metabolic memory' that protects against obesity.
This research highlights the potential of targeting GIPR in fat cells for developing new obesity treatments, offering hope for more effective therapies beyond current GLP-1R focused drugs. The study was funded by grants from Eli Lilly and Co. and the National Institutes of Health, underscoring the importance of this discovery in the fight against obesity and its associated health risks.
