Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin
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.
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Diets with increased saturated fat content, or exposure of cultured cells to saturated FA, promote apoptosis, which can be reversed by the addition of mono- or polyunsaturated FA.
“Studies examining the effects of altering dietary FA composition have suggested that diets with increased saturated fat content, or exposure of cultured cells to saturated FA promote apoptosis, which can be reversed by the addition of mono- or polyunsaturated FA (PUFA) (74, 212, 236, 260).”
From Cardiac remodeling in obesity (2008) · cites this paper as [260]
A diet high in saturated fat is associated with increased triglyceride and ceramide concentrations that correlate with an increase in apoptosis.
“Moreover, a diet that was high in saturated fat was associated with increased triglyceride and ceramide concentrations that correlated with an increase in apoptosis (260).”
From Cardiac remodeling in obesity (2008) · cites this paper as [260]
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- Authors
- 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.
- Affiliations
- Case Western Reserve University (US)
- Henry Ford Health (US)
- Baylor College of Medicine (US)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2006-07
- Volume
- 291
- Issue
- 1
- Pages
- H38-H44
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2118968865
- Cited by
- 147
- References
- 47
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 4 · 2014: 14 · 2013: 11 · 2012: 10
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 074237, HL-074259, P01HL074237, R01HL074259)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- saturated fatty acids, unsaturated fatty acids, high-fat diet, cardiomyocyte apoptosis, ceramide, peroxisome proliferator-activated receptors, leptin, insulin, UCP3, PDK4, medium-chain acyl-CoA dehydrogenase, cardiac fatty acid metabolism, cardiac function
- MeSH terms
- Adipose Tissue, Animals, Body Constitution, Body Weight, Cells, Cultured, Dietary Fats, Dietary Fats, Unsaturated, Fatty Acids, Male, Rats, Wistar, Apoptosis, Leptin, Myocytes, Cardiac, Rats
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