INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

Preferential Oxidation of Triacylglyceride-Derived Fatty Acids in Heart Is Augmented by the Nuclear Receptor PPAR{alpha}

Show full item record

Bookmark or cite this item: http://hdl.handle.net/10027/7585

Files in this item

File Description Format
PDF 233.pdf (421KB) (no description provided) PDF
Title: Preferential Oxidation of Triacylglyceride-Derived Fatty Acids in Heart Is Augmented by the Nuclear Receptor PPAR{alpha}
Author(s): Banke, Natasha H.; Wende, Adam R.; Leone, Teresa C.; O'Donnell, Michael; Abel, E. Dale; Kelly, Daniel P.; Lewandowski, E. Douglas
Subject(s): triacylglyceride PPAR(alpha)
Abstract: Rationale: Long chain fatty acids (LCFAs) are the preferred substrate for energy provision in hearts. However, the contribution of endogenous triacylglyceride (TAG) turnover to LCFA oxidation and the overall dependence of mitochondrial oxidation on endogenous lipid is largely unstudied. Objective: We sought to determine the role of TAG turnover in supporting LCFA oxidation and the influence of the lipid-activated nuclear receptor, proliferator-activated receptor (PPAR), on this balance. Methods and Results: Palmitoyl turnover within TAG and palmitate oxidation rates were quantified in isolated hearts, from normal mice (nontransgenic) and mice with cardiac-specific overexpression of PPAR (MHC-PPAR). Turnover of palmitoyl units within TAG, and thus palmitoyl-coenzyme A recycling, in nontransgenic (4.5±2.3 µmol/min per gram dry weight) was 3.75-fold faster than palmitate oxidation (1.2±0.4). This high rate of palmitoyl unit turnover indicates preferential oxidation of palmitoyl units derived from TAG in normal hearts. PPAR overexpression augmented TAG turnover 3-fold over nontransgenic hearts, despite similar fractions of acetyl-coenzyme A synthesis from palmitate and oxygen use at the same workload. Palmitoyl turnover within TAG of MHC-PPAR hearts (16.2±2.9, P<0.05) was 12.5-fold faster than oxidation (1.3±0.2). Elevated TAG turnover in MHC-PPAR correlated with increased mRNA for enzymes involved in both TAG synthesis, Gpam (glycerol-3-phosphate acyltransferase, mitochondrial), Dgat1 (diacylglycerol acetyltransferase 1), and Agpat3 (1-acylglycerol-3-phospate O-acyltransferase 3), and lipolysis, Pnliprp1 (pancreatic lipase related protein 1). Conclusions: The role of endogenous TAG in supporting β-oxidation in the normal heart is much more dynamic than previously thought, and lipolysis provides the bulk of LCFA for oxidation. Accelerated palmitoyl turnover in TAG, attributable to chronic PPAR activation, results in near requisite oxidation of LCFAs from TAG.
Issue Date: 2010-07-23
Publisher: American Heart Association
Citation Info: Banke, N. H., Wende, A. R., Leone, T. C., O'Donnell, J. M., Abel, E. D., Kelly, D. P., & Lewandowski, E. D. 2010. Preferential Oxidation of Triacylglyceride-Derived Fatty Acids in Heart Is Augmented by the Nuclear Receptor PPAR{alpha}. Circulation Research. DOI: 10.1161/CIRCRESAHA.110.221713
Type: Article
Description: The original source for this publication is at the American Heart Association; DOI: 10.1161/CIRCRESAHA.110.221713
URI: http://hdl.handle.net/10027/7585
ISSN: 0009-7330
Sponsor: This work is supported by NIH grants R37HL49244, R01HL62702, and T32HL07692.
Date Available in INDIGO: 2011-05-07
 

This item appears in the following Collection(s)

Show full item record

Statistics

Country Code Views
United States of America 155
China 20
United Kingdom 14
Germany 6
Russian Federation 4

Browse

My Account

Information

Access Key