ESPEYB21 11. Obesity and Weight Regulation Interventions for Weight Loss: New Findings (5 abstracts)
11.5. Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor
Regmi A , Aihara E , Christe ME , Varga G , Beyer TP , Ruan X , Beebe E , O’Farrell LS , Bellinger MA , Austin AK , Lin Y , Hu H , Konkol DL , Wojnicki S , Holland AK , Friedrich JL , Brown RA , Estelle AS , Badger HS , Gaidosh GS , Kooijman S , Rensen PCN , Coskun T , Thomas MK & Roell W
Eli Lilly and Company, Indianapolis, IN 46285, USA. bill_roell@lilly.com
Cell Metab 2024 36(7): 1534-1549.e7. doi:10.1016/j.cmet.2024.05.010. https://pubmed.ncbi.nlm.nih.gov/38878772.
Brief Summary: The study investigated how tirzepatide, a dual GIPR/GLP-1R agonist, modulates adipocyte nutrient metabolism by long-acting activation of the GIP receptor. It shows that tirzepatide enhances insulin signaling, glucose uptake, and lipid metabolism in adipocytes, contributing to improved metabolic outcomes in both fasted and fed states.
Tirzepatide has recently been shown to have superior efficacy in reducing HbA1c, body weight, and serum triglycerides compared to selective GLP-1R agonists1. Prior studies demonstrated that GLP1R is not primarily expressed on adipocytes. The current study provides substantial evidence of GIPR expression and functional activation in adipocytes, highlighting a significant role in adipocyte metabolism regulation. The regulation of key metabolic transcription factors and pathways by tirzepatide aligns with existing knowledge on the importance of these pathways in maintaining metabolic homeostasis. These findings add depth by demonstrating the specific contributions of GIPR agonism and advance the understanding of tirzepatide’s role in adipocyte nutrient metabolism and its superior clinical efficacy. By elucidating the dual mechanisms of GIPR and GLP-1R agonism, this research provides a robust framework for the development of more effective treatments for T2D and obesity.
Reference: 1. Frías, J. P., Davies, M. J., Rosenstock, J., Pérez, Manghi, F. C., Fernández, Landó, L, Bergman, B. K., Liu, B., Cui, X., & Brown K. (2021). Tirzepatide, versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine, 385(6), 503–515. https://doi.org/10.1056/nejmoa2107519.
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