Analysis of the Sphingolipidome in NAFLD

The relationship between sphingolipid levels and NAFLD pathology has been recognized for some time. Numerous studies using pharmacological and genetic approaches in vitro and in animal models of NAFLD have demonstrated that modifications to sphingolipid metabolism can attenuate various facets of NAFLD pathology. However, a more precise understanding of the role of sphingolipids and NAFLD pathology is essential to creating therapeutics that target this pathway. This chapter touches on the scale and variety of sphingolipid metabolites at play in NAFLD, which vary widely in their chemical structures and biological functions. With advances in liquid chromatography and tandem mass spectrometry approaches, each of thousands of individual sphingolipid species and sphingolipid metabolites can be identified and precisely quantified. These approaches are beginning to reveal specific sub-classes and species of sphingolipids that change in NAFLD, and as such, enzymes that generate them can be identified and potentially serve as therapeutic targets. Advances in lipidomics technology have been, and will continue to be, critical to these gains in our understanding of NAFLD.