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Circ Heart Fail. 2013 May;6(3):550-62. doi: 10.1161/CIRCHEARTFAILURE.112.000177. Epub 2013 Apr 9.

Peroxisome proliferator-activated receptor-γ activation prevents sepsis-related cardiac dysfunction and mortality in mice.

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Division of Preventive Medicine and Nutrition, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.



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.


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.


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


PPAR; cardiac metabolism; fatty acids; sepsis

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