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Updated: Jul 30, 2025
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Tirzepatide attenuates lipopolysaccharide-induced left ventricular remodeling and dysfunction by inhibiting the
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 430060, Hubei, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei, PR China.
Backgrounds:
Sepsis-induced cardiac dysfunction is a leading cause of mortality in intensive care units. Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, possess cardio-protective, their effects on sepsis-induced cardiomyopathy remain unknown.
Methods:
C57BL/6 mice received subcutaneous injections of tirzepatide once a day for 14 days before subjected to LPS challenge for 12 h. LPS-induced cardiac dysfunction and its potential mechanisms were estimated by pathological analysis, echocardiographic measurement, electrocardiography, langendorff-perfused heart and molecular analysis.
Results:
Pretreatment with tirzepatide attenuates LPS-induced cardiac dysfunction. tirzepatide remarkably reduces LPS-mediated inflammatory responses by inhibiting the cardiac protein levels of TNF-α, IL-6, and IL-1B in mice. Interestingly, tirzepatide administration also improves cardiomyocytes apoptosis caused by LPS treatment. Furthermore, the protective roles of irzepatide against LPS-mediated increased inflammatory responses and decreased cardiomyocytes apoptosis are partially blunted by inhibiting TLR4/NF-kB/NLRP3 inflammation signaling. In addition, tirzepatide reduce the susceptibility ventricular arrhythmia in LPS-treated mice.
Conclusion:
In brief, tirzepatide attenuates LPS-induced left ventricular remodeling and dysfunction by inhibiting the TLR4/NF-kB/NLRP3 pathway.
