Lipids regulated by exercise and phosphoinositide 3-kinase: potential role as biomarkers and therapeutic targets for cardiovascular disease

Lipids are organic biomolecules that provide structural support to cells, but are also important for energy storage and signaling. Lipid profiling has emerged as a new technology with the potential of identifying new biomarkers and therapeutic targets. The lipid composition of cardiomyocyte membranes is altered during the process of cardiac remodeling, including exercise-induced heart enlargement (physiological cardiac hypertrophy) and disease-induced pathological remodeling. Phosphoinositide 3-kinase (PI3K) is an essential regulator of exercise-induced physiological hypertrophy and mediator of cardioprotection in cardiac stress settings. In this review, we first briefly summarize the protective role of exercise and PI3K on the heart. Next, we describe the regulation of lipids in the heart and circulation by exercise or transgenic expression of PI3K (increased or decreased), and contrast this to cardiac disease settings. We also describe studies in which exercise or PI3K-regulated lipids have been associated with cardiorespiratory fitness or cardioprotection, and discuss potential clinical applications.