Journal article
Preferential Oxidation of Triacylglyceride-Derived Fatty Acids in Heart Is Augmented by the Nuclear Receptor PPARα
Circulation research, Vol.107(2), pp.233-241
2010
DOI: 10.1161/CIRCRESAHA.110.221713
PMCID: PMC2921193
PMID: 20522803
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)alpha, 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 PPARalpha (MHC-PPARalpha). Turnover of palmitoyl units within TAG, and thus palmitoyl-coenzyme A recycling, in nontransgenic (4.5+/-2.3 micromol/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. PPARalpha 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-PPARalpha hearts (16.2+/-2.9, P<0.05) was 12.5-fold faster than oxidation (1.3+/-0.2). Elevated TAG turnover in MHC-PPARalpha 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 beta-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 PPARalpha activation, results in near requisite oxidation of LCFAs from TAG.
Details
- Title: Subtitle
- Preferential Oxidation of Triacylglyceride-Derived Fatty Acids in Heart Is Augmented by the Nuclear Receptor PPARα
- Creators
- Natasha H BANKE - Program in Integrative Cardiac Metabolism Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, United StatesAdam R WENDE - Sanford-Burnham Medical Research Institute, Orlando, Fla, United StatesTeresa C LEONE - Division of Endocrinology Metabolism and Diabetes and Program in Molecular Medicine University of Utah School of Medicine, Salt Lake City, United StatesJ. Michael O'DONNELL - Program in Integrative Cardiac Metabolism Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, United StatesE Dale Abel - Program in Integrative Cardiac Metabolism Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, United StatesDaniel P KELLY - Division of Endocrinology Metabolism and Diabetes and Program in Molecular Medicine University of Utah School of Medicine, Salt Lake City, United StatesE. Douglas LEWANDOWSKI - Sanford-Burnham Medical Research Institute, Orlando, Fla, United States
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.107(2), pp.233-241
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- DOI
- 10.1161/CIRCRESAHA.110.221713
- PMID
- 20522803
- PMCID
- PMC2921193
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025296102771
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