Abstract
Fatty acids (FAs) have structural and functional diversity. FAs in the heart are closely associated with cardiac function, and their qualitative or quantitative abnormalities lead to the onset and progression of cardiac disease. FAs are important as an energy substrate for the heart, but when in excess, they exhibit cardio-lipotoxicity that causes cardiac dysfunction or heart failure with preserved ejection fraction. FAs also play a role as part of phospholipids that compose cell membranes, and the changes in mitochondrial phospholipid cardiolipin and the FA composition of plasma membrane phospholipids affect cardiomyocyte survival. In addition, FA metabolites exert a wide variety of bioactivities in the heart as lipid mediators. Recent advances in measurement using mass spectrometry have identified trace amounts of n-3 polyunsaturated fatty acids (PUFAs)-derived bioactive metabolites associated with heart disease. n-3 PUFAs have a variety of cardioprotective effects and have been shown in clinical trials to be effective in cardiovascular diseases, including heart failure. This review outlines the contributions of FAs to cardiac function and pathogenesis of heart diseases from the perspective of three major roles and proposes therapeutic applications and new medical perspectives of FAs represented by n-3 PUFAs.
Highlights
FA oxidation (FAO) does not increase in heart failure with preserved fraction (HFpEF) [16]. These results suggest that FAO is not adaptively activated, and abnormal lipid accumulation occurs in cardiomyocytes, which induces cardiotoxicity and contributes to the appearance of HFpEF
Several reports have shown the differential effects of saturated Fatty acids (FAs) and monounsaturated FA on cellular and cardiac function [32,33], while desaturation enzymes are associated with heart disease
We summarize various clinical trials using n-3 polyunsaturated fatty acids (PUFAs), provide an overview of studies that elucidated the molecular mechanism of n-3 PUFAs in the pathogenesis of cardiovascular diseases, and discuss the differences between EPA and docosahexaenoic acid (DHA)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Many lipids are subjected to precise enzymatic control to maintain the homeostasis of tissues in living organisms, and it is important to regulate the qualitative and quantitative balance of lipids in the heart. Alterations in lipid composition and structural remodeling of membrane lipids occur mainly through changes in the expression of enzymes related to lipid synthesis, metabolism, remodeling, and oxidation. The changes in the cardiac lipid profile act pathologically or compensatory to heart injury and characterize heart failure. Fatty acids (FAs) are used as (1) energy sources, (2) components of membrane phospholipids, and (3) bioactive mediators. From the point of view of these three major roles, we introduce and discuss the recent advances in understanding lipid dynamics, especially focusing on FA changes in heart failure
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