Thumbnail
Access Restriction
Open

Author Xia, Congying ♦ Dong, Ruolan ♦ Chen, Chen ♦ Wang, Hong ♦ Wang, Dao Wen
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ CARBOXYLIC ACIDS ♦ ESCHERICHIA COLI ♦ GLUCOSE ♦ HEART ♦ LIPOPOLYSACCHARIDES ♦ METABOLISM ♦ MORTALITY ♦ OXIDATION ♦ RECEPTORS ♦ TRANSGENIC MICE
Abstract Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i.p.) and myocardial function was assessed 6 h later using echocardiography and hemodynamics. Deteriorated cardiac function evidenced by reduction of the percentage of left ventricular ejection fraction and fractional shortening after LPS administration was significantly attenuated by cardiomyocyte specific expression of ACOT1. αMHC-ACOT1 mice exhibited a markedly increase in glucose utilization and cardiac FAO compared with LPS-treated WT mice. Suppression of cardiac peroxisome proliferator activated receptor alpha (PPARa) and PPARγ-coactivator-1α (PGC1a) signaling observed in LPS-challenged WT mice was activated by the presence of ACOT1. These results suggest that ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction, possibly through activating PPARa/PGC1a signaling. - Highlights: • ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction. • ACOT1 can regulate PPARa/PGC1a signaling pathway. • We first generate the transgenic mice with cardiomyocyte specific expression of ACOT1.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-12-25
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 468
Issue Number 4


Open content in new tab

   Open content in new tab