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A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction
Published on: March 29, 2024
Linoleate-rich high-fat diet decreases mortality in hypertensive heart failure rats compared with lard and low-fat
Adam J Chicco1, Genevieve C Sparagna, Sylvia A McCune
1Department of Integrative Physiology, University of Colorado Cardiovascular Research Institute, University of Colorado, Boulder, USA. chicco@cahs.colostate.edu
Insights
High-fat diets impact heart disease prognosis differently based on fatty acid composition. Linoleate-rich diets may improve survival in advanced hypertensive heart disease, while lard-based diets hasten mortality.
Area of Science:
- Cardiology
- Nutritional Science
- Gerontology
Background:
- High-fat diets may reduce cardiac hypertrophy and dysfunction in hypertension.
- Prognostic effects of high-fat diets in aged individuals with advanced hypertensive heart disease remain unclear.
- Fatty acid composition's role in modulating these effects requires investigation.
Purpose of the Study:
- To investigate the impact of high-fat diet composition on disease progression and mortality in aged rats with advanced hypertensive heart failure.
- To compare the effects of high-linoleate safflower oil and lard diets against a high-carbohydrate diet.
Main Methods:
- Aged spontaneously hypertensive heart failure rats were fed either a high-carbohydrate diet, a high-fat diet with high-linoleate safflower oil, or a high-fat diet with lard until death.
- Cardiac morphology, function, and mortality were assessed.
- Myocardial fatty acid profiles, thromboxane excretion, and blood pressure were analyzed.
Main Results:
- Both high-fat diets attenuated cardiac hypertrophy, left ventricular dilation, and systolic dysfunction compared to the high-carbohydrate diet.
- The lard diet significantly increased mortality, while the linoleate diet significantly delayed mortality.
- Linoleate-enriched diets increased myocardial cardiolipin content, a phospholipid deficient in failing hearts.
Conclusions:
- Dietary fatty acid composition critically influences mortality in advanced hypertensive heart disease, despite potential benefits on cardiac structure and function.
- Linoleate-rich diets may offer a survival advantage, potentially via cardiolipin enrichment.
- Further research is needed to elucidate the mechanisms behind these divergent effects.
Abstract:
Recent studies indicate that high-fat diets may attenuate cardiac hypertrophy and contractile dysfunction in chronic hypertension. However, it is unclear whether consuming a high-fat diet improves prognosis in aged individuals with advanced hypertensive heart disease or the extent to which differences in its fatty acid composition modulate its effects in this setting. In this study, aged spontaneously hypertensive heart failure rats were administered a standard high-carbohydrate diet or high-fat diet (42% of kilocalories) supplemented with high-linoleate safflower oil or lard until death to determine their effects on disease progression and mortality. Both high-fat diets attenuated cardiac hypertrophy, left ventricular chamber dilation, and systolic dysfunction observed in rats consuming the high-carbohydrate diet. However, the lard diet significantly hastened heart failure mortality compared with the high-carbohydrate diet, whereas the linoleate diet significantly delayed mortality. Both high-fat diets elicited changes in the myocardial fatty acid profile, but neither had any effect on thromboxane excretion or blood pressure. The prosurvival effect of the linoleate diet was associated with a greater myocardial content and linoleate-enrichment of cardiolipin, an essential mitochondrial phospholipid known to be deficient in the failing heart. This study demonstrates that, despite having favorable effects on cardiac morphology and function in hypertension, a high-fat diet may accelerate or attenuate mortality in advanced hypertensive heart disease depending on its fatty acid composition. The precise mechanisms responsible for the divergent effects of the lard and linoleate-enriched diets merit further investigation but may involve diet-induced changes in the content and/or composition of cardiolipin in the heart.
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