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Am J Physiol Heart Circ Physiol 291: H38-H44, 2006. First published January 27, 2006; doi:10.1152/ajpheart.01295.2005
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TRANSLATIONAL PHYSIOLOGY

Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin

Isidore C. Okere,1 Margaret P. Chandler,1 Tracy A. McElfresh,1 Julie H. Rennison,1 Victor Sharov,4 Hani N. Sabbah,4 Kou-Yi Tserng,2 Brian D. Hoit,3 Paul Ernsberger,2 Martin E. Young,5 and William C. Stanley1,2

Departments of 1Physiology and Biophysics, 2Nutrition, and 3Medicine, Case Western Reserve University, Cleveland, Ohio; 4Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan; and 5Department of Pediatrics, Baylor College of Medicine, Houston, Texas

Submitted 8 December 2005 ; accepted in final form 24 January 2006

Fatty acids are the primary fuel for the heart and are ligands for peroxisome proliferator-activated receptors (PPARs), which regulate the expression of genes encoding proteins involved in fatty acid metabolism. Saturated fatty acids, particularly palmitate, can be converted to the proapoptotic lipid intermediate ceramide. This study assessed cardiac function, expression of PPAR-regulated genes, and cardiomyocyte apoptosis in rats after 8 wk on either a low-fat diet [normal chow control (NC); 10% fat calories] or high-fat diets composed mainly of either saturated (Sat) or unsaturated fatty acids (Unsat) (60% fat calories) (n = 10/group). The Sat group had lower plasma insulin and leptin concentrations compared with the NC or Unsat groups. Cardiac function and mass and body mass were not different. Cardiac triglyceride content was increased in the Sat and Unsat groups compared with NC (P < 0.05); however, ceramide content was higher in the Sat group compared with the Unsat group (2.9 ± 0.2 vs. 1.4 ± 0.2 nmol/g; P < 0.05), whereas the NC group was intermediate (2.3 ± 0.3 nmol/g). The number of apoptotic myocytes, assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining, was higher in the Sat group compared with the Unsat group (0.28 ± 0.05 vs. 0.17 ± 0.04 apoptotic cells/1,000 nuclei; P < 0.04) and was positively correlated to ceramide content (P < 0.02). Both high-fat diets increased the myocardial mRNA expression of the PPAR-regulated genes encoding uncoupling protein-3 and pyruvate dehydrogenase kinase-4, but only the Sat diet upregulated medium-chain acyl-CoA dehydrogenase. In conclusion, dietary fatty acid composition affects cardiac ceramide accumulation, cardiomyocyte apoptosis, and expression of PPAR-regulated genes independent of cardiac mass or function.

ceramide; fatty acids; heart; lipotoxicity; mitochondria; obesity


Address for reprint requests and other correspondence: W. C. Stanley, Dept. of Physiology and Biophysics, School of Medicine, Case Western Reserve Univ., 10900 Euclid Ave., Cleveland, OH 44106-4970 (e-mail: wcs4{at}case.edu)




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