Submitted to: American Journal of Physiology - Heart and Circulatory Physiology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/24/2006
Publication Date: 7/1/2006
Citation: Okere, I.C., Chandler, M.P., McElfresh, T.A., Rennison, J.H., Sharov, V., Sabbah, H.N., Tserng, K.Y., Hoit, B.D., Ernsberger, P., Young, M.E., Stanley, W.C. 2006. Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin. American Journal of Physiology - Heart and Circulatory Physiology. 291(1):H38-H44. Interpretive Summary: It has been known for some time that certain fatty acids increase the risk of heart disease (for example, fat from meat is rich in saturated fatty acids), while others appear to be beneficial (for example, olive oil is rich in unsaturated fatty acids). The reasons for these observations are unclear. The present study investigated whether feeding rats a diet rich in saturated fatty acids affected the heart differently compared to feeding rats a diet rich in unsaturated fatty acids. The results show that the saturated fatty acid diet was more toxic to the heart, compared to unsaturated fatty acids. For example, the saturated fatty acid diet caused a higher proportion of heart cells to spontaneously die, compared to the unsaturated fatty acid diet.
Technical Abstract: 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.