Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210, USA.
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Department of Medicine, Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Molecular Probes Inc., Eugene, OR 97402, USA.
Department of Chemistry, University of Washington, Seattle, WA 98133, USA.
Zebrafish are a valuable model for mammalian lipid metabolism; larvae process lipids similarly through the intestine and hepatobiliary system and respond to drugs that block cholesterol synthesis in humans. After ingestion of fluorescently quenched phospholipids, endogenous lipase activity and rapid transport of cleavage products results in intense gall bladder fluorescence. Genetic screening identifies zebrafish mutants, such as fat free, that show normal digestive organ morphology but severely reduced phospholipid and cholesterol processing. Thus, fluorescent lipids provide a sensitive readout of lipid metabolism and are a powerful tool for identifying genes that mediate vertebrate digestive physiology.