Lipidomic Profiles of the Heart and Circulation in Response to Exercise versus Cardiac Pathology: A Resource of Potential Biomarkers and Drug Targets

Abstract

Exercise-induced heart growth provides protection against cardiovascular disease, whereas disease-induced heart growth leads to heart failure. These distinct forms of growth are associated with different molecular profiles (e.g., mRNAs, non-coding RNAs, and proteins), and targeting differentially regulated genes has therapeutic potential for heart failure. The effects of exercise on the cardiac and circulating lipidomes in comparison to disease are unclear. Lipidomic profiling was performed on hearts and plasma of mice subjected to swim endurance training or a cardiac disease model (moderate or severe pressure overload). Several sphingolipid species and phospholipids containing omega-3/6 fatty acids were distinctly altered in heart and/or plasma with exercise versus pressure overload. A subset of lipids was validated in an independent mouse model with heart failure and atrial fibrillation. This study highlights the adaptations that occur to lipid profiles in response to endurance training versus pathology and provides a resource to investigate potential therapeutic targets and biomarkers.

LipidCreator workbench to probe the lipidomic landscape

“…Supplementing the fully accessible workbench, we also prepared predefined transition lists for several model system lipidomes, such as yeast, mouse (platelets, heart, brain hippocampus), drosophila and human (plasma, platelets) [32][33][34][35][36] , making it straightforward to start a targeted lipidomics experiment.…”

“…To the best of our knowledge, due to the lack of isotope-coded standards there are currently no large-scale methods available to cope with occurring stereoisomers. The isomers existence and quantity should be reported individually based on their retention time 35 or summed up and reported as one species as it was done here and in previous studies 14,51 . In the end, the user has to decide whether these issues pose a potential challenge for their analysis regarding a specific chromatographic setup, target MS platform and acquisition scheme.…”

Acarbose has sex-dependent and -independent effects on age-related physical function, cardiac health, and lipid biology

“…Accumulation of TAGs in the heart occurs with atherosclerosis and related risk factors (i.e., obesity and T2DM), which can induce cardiac lipotoxicity and impair cardiomyocyte structure and function (54). The slowing of age-associated changes in PCs and fatty acids may also provide benefits to cardiac health in aging males, particularly given the role of fatty acids as the primary cardiac metabolic fuel source and the structural alterations in PCs that occur with pathological cardiac hypertrophy (55). Taken together, our data suggest that ACA may play a beneficial role in preserving lipid utilization and cardiac structure, leading to improved cardiac health and function over time.…”

Big Data Approaches in Heart Failure Research

“…[10,11] Bulk The agnostic or targeted study of metabolites. Reviewed in [19] Lipidomics The study of the complete or targeted lipid profile in an individual or population [20,21] Wearables An item worn externally that provides continuous data on parameters like heart rate, blood pressure, or fitness activity.…”