• Konstantinos Drosatos, Raffay S Khan, Chad M Trent, Hongfeng Jiang, Ni-Huiping Son, William S Blaner, Shunichi Homma, P Christian Schulze, and Ira J Goldberg.
• Division of Preventive Medicine and Nutrition, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. kd2277@columbia.edu
• Circ Heart Fail. 2013 May 1;6(3):550-62.

BackgroundCardiac 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 ResultsEscherichia 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.ConclusionsActivation of PPARγ in LPS-treated mice prevented cardiac dysfunction and mortality, despite development of cardiac inflammation and PPARα downregulation.

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