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

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


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.

Keywords: PPAR; cardiac metabolism; fatty acids; sepsis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fatty Acids / metabolism
  • Heart Diseases / mortality
  • Heart Diseases / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocardium / metabolism
  • PPAR gamma / agonists
  • PPAR gamma / metabolism*
  • Rosiglitazone
  • Sepsis / complications*
  • Sepsis / physiopathology
  • Sepsis / therapy
  • Thiazolidinediones / pharmacology
  • Ventricular Dysfunction, Left / physiopathology


  • Fatty Acids
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone