Shotgun lipidomics of neutral lipids as an enabling technology for elucidation of lipid-related diseases

Neutral lipids fulfill multiple specialized roles in cellular function. These roles include energy storage and utilization, the synthesis of complex lipids in cellular membranes, lipid second messengers for cellular signaling, and the modulation of membrane molecular dynamics. We have developed a novel mass spectrometric technology, now termed shotgun lipidomics, that can identify the types and amounts of thousands of lipids directly from extracts of biological samples. Shotgun lipidomics is well suited for the identification and measurement of the types and amounts of neutral lipid classes and individual molecular species through the use of multidimensional mass spectrometry. This review summarizes the basic principles underlying the use of shotgun lipidomics for the direct measurement of neutral lipids from extracts of biological tissues or fluids. Through exploiting the high information content inherent in shotgun lipidomics, this technology promises to greatly facilitate advances in our understanding of alterations in neutral lipid metabolism in health and disease.