Effects of chronic activation of peroxisome proliferator-activated receptor-α or high-fat feeding in a rat infarct model of heart failure
Abstract
Intracardiac accumulation of lipid and related intermediates (e.g., ceramide) is associated with cardiac dysfunction and may contribute to the progression of heart failure (HF). Overexpression of nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) increases intramyocellular ceramide and left ventricular (LV) dysfunction. We tested the hypothesis that activation of fatty acid metabolism with fat feeding or a PPARα agonist increases myocardial triglyceride and/or ceramide and exacerbates LV dysfunction in HF. Rats with infarct-induced HF ( n = 38) or sham-operated rats ( n = 10) were either untreated (INF, n = 10), fed a high-fat diet (45% kcal fat, INF + Fat, n = 15), or fed the PPARα agonist fenofibrate (150 mg·kg−1·day−1, INF + Feno, n = 13) for 12 wk. LV ejection fraction was significantly reduced with HF (49 ± 6%) compared with sham operated (86 ± 2%) with no significant differences in ejection fraction (or other functional or hemodynamic measures) among the three infarcted groups. Treatment with the PPARα agonist resulted in LV hypertrophy (24% increase in LV/body mass ratio) and induced mRNAs encoding for PPARα-regulated genes, as well as protein expression and activity of medium chain acyl-CoA dehydrogenase (compared with INF and INF + Fat groups). Myocardial ceramide content was elevated in the INF group compared with sham-operated rats, with no further change in the INF + Fat or INF + Feno groups. Myocardial triglyceride was unaffected by infarction but increased in the INF + Fat group. In conclusion, LV dysfunction and dilation are not worsened despite upregulation of the fatty acid metabolic pathway and LV hypertrophy or accumulation of myocardial triglyceride in the rat infarct model of HF.
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Isocaloric high-fat diets that are associated with reduced levels of insulin and leptin appear to attenuate LV hypertrophy in pressure overload hypertrophy and minimize LV remodeling in a rat infarct model.
“For example, isocaloric high-fat diets that are associated with reduced levels of insulin and leptin appear to attenuate LV hypertrophy in pressure overload hypertrophy and minimize LV remodeling in a rat infarct model (239, 261, 262).”
From Cardiac remodeling in obesity (2008) · cites this paper as [239]
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- Authors
- Morgan, E. E., Rennison, J. H., Young, M. E., McElfresh, T. A., Kung, T. A., Tserng, K.-Y., Hoit, B. D., Stanley, W. C., & Chandler, M. P.
- Affiliations
- Case Western Reserve University (US)
- Baylor College of Medicine (US)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2006-05
- Volume
- 290
- Issue
- 5
- Pages
- H1899-H1904
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2112061410
- Cited by
- 86
- References
- 38
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 7 · 2014: 4 · 2013: 5 · 2012: 3
- FWCI
- 3.78
- 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-074259, P01HL074237, HL-74237, R01HL074259)
- Topics
- 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
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- heart failure, myocardial infarction, PPARα, fenofibrate, high-fat diet, ceramide, myocardial triglycerides, left ventricular dysfunction, left ventricular hypertrophy, fatty acid metabolism, acyl-CoA dehydrogenase, myocardial lipid accumulation
- MeSH terms
- Animals, Hypolipidemic Agents, Ceramides, Dietary Fats, Disease Models, Animal, Feeding Behavior, Heart Failure, Male, Myocardial Infarction, Fenofibrate, Time Factors, Up-Regulation, Treatment Outcome, Rats, Wistar, Ventricular Dysfunction, Left, PPAR alpha, Rats
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