In the May 18 Science, Farber et al. report the use of fluorescently quenched phospholipid substrates to screen for genes affecting lipid metabolism in living zebrafish larvae (Science 2001, 292:1385-1388). The lipids were swallowed by the larvae and cleaved by lipases in the intestine before the fluorescent metabolites were transported to the liver and gall bladder. The assay demonstrated lipid metabolism defects in zebrafish mutants that have abnormal digestive organ morphology, as well as the 'fat free' mutant that has an apparently normal digestive tract appearance. The authors suggest that the fat free mutation affects bile synthesis or secretion. This combination of mutagenesis screens with simple imaging of enzymatic function in vivo should provide insights into human lipid metabolism disorders.

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