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Updated: May 12, 2026
Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
Peroxisome proliferator-activated receptor-γ activation prevents sepsis-related cardiac dysfunction and mortality in
Konstantinos Drosatos1, Raffay S Khan, Chad M Trent
1Division of Preventive Medicine and Nutrition, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. kd2277@columbia.edu
Background:
Cardiac dysfunction with sepsis is associated with both inflammation and reduced fatty acid oxidation. We hypothesized that energy deprivation accounts for sepsis-related cardiac dysfunction.
Methods And Results:
Escherichia coli lipopolysaccharide (LPS) administered to C57BL/6 mice (wild type) induced cardiac dysfunction and reduced fatty acid oxidation and mRNA levels of peroxisome proliferator-activated receptor (PPAR)-α and its downstream targets within 6-8 hours. Transgenic mice in which cardiomyocyte-specific expression of PPARγ is driven by the α-myosin heavy chain promoter (αMHC-PPARγ) were protected from LPS-induced cardiac dysfunction. Despite a reduction in PPARα, fatty acid oxidation and associated genes were not decreased in hearts of LPS-treated αMHC-PPARγ mice. LPS treatment, however, continued to induce inflammation-related genes, such as interleukin-1α, interleukin-1β, interleukin-6, and tumor necrosis factor-α in hearts of αMHC-PPARγ mice. Treatment of wild-type mice with LPS and the PPARγ agonist, rosiglitazone, but not the PPARα agonist (WY-14643), increased fatty acid oxidation, prevented LPS-mediated reduction of mitochondria, and treated cardiac dysfunction, as well as it improved survival, despite continued increases in the expression of cardiac inflammatory markers.
Conclusions:
Activation of PPARγ in LPS-treated mice prevented cardiac dysfunction and mortality, despite development of cardiac inflammation and PPARα downregulation.
