Measurement of lipid flux to advance translational research: evolution of classic methods to the future of precision health

Over the past 70 years, the study of lipid metabolism has led to important discoveries in identifying the underlying mechanisms of chronic diseases. Advances in the use of stable isotopes and mass spectrometry in humans have expanded our knowledge of target molecules that contribute to pathologies and lipid metabolic pathways. These advances have been leveraged within two research paths, leading to the ability (1) to quantitate lipid flux to understand the fundamentals of human physiology and pathology and (2) to perform untargeted analyses of human blood and tissues derived from a single timepoint to identify lipidomic patterns that predict disease. This review describes the physiological and analytical parameters that influence these measurements and how these issues will propel the coming together of the two fields of metabolic tracing and lipidomics. The potential of data science to advance these fields is also discussed. Future developments are needed to increase the precision of lipid measurements in human samples, leading to discoveries in how individuals vary in their production, storage, and use of lipids. New techniques are critical to support clinical strategies to prevent disease and to identify mechanisms by which treatments confer health benefits with the overall goal of reducing the burden of human disease. Lipid metabolism: tracking lipid and precision medicine Personalized tracking of how lipid (fat) metabolism changes over time could lead to improvements in the diagnosis and treatment of several diseases. Elizabeth Parks and colleagues from the University of Missouri, Columbia, USA, discuss the ways in which researchers use stable isotope labeling to monitor the kinetics of fatty acids and other lipids in the body. Usually, lipid quantities are measured only at a single timepoint, however the tracking of lipid turnover over time provides further diagnostic information. Aided by new techniques such as high-throughput mass spectrometry and machine learning, researchers are now able to continuously map total lipid contents in individual patients. The transition of measurements of lipid flux from the research laboratory to the doctor’s office will likely play a role in a new era of precision medicine.