Model Organisms in Drug Discovery

the embryo media containing radioactive lipids with or without statins. Here,
we show one example of our lipomics study using 14 C-oleic acid labeling with
Drug A (20 h of treatment). We first found that Drug A interferes with
fluorescent reporters in live zebrafish larvae as described above, then we went
on to study 14 C-oleic acid labeling. The results showed that Drug A
significantly decreased phosphatidylcholine synthesis and that most radioactivities
remained in the fatty acid fraction for the Drug A treatment group
(Figure 8.4). This suggests that Drug A may interfere with the phospholipid
synthesis pathway. By combining these two high-throughput techniques we
can perform large-scale screening of the chemical compounds that perturb
lipid metabolism in zebrafish larvae and gain some information about the
pathway by which these compounds interfere.
Screening strategies
LIPID METABOLISM SCREEN 211
Figure 8.4 Lipomics analysis. Larvae (5 days post-fertilization) were incubated with
radioactive oleic acid for 20 h, followed by lipid extraction and thin-layer chromatography
(TLC). The solvent chloroform–ethanol–triethylamine–water (30:34:30:8) was used to
develop the TLC plate. The radioactivities were scanned. The major metabolites derived
from oleic acid (FA) are phosphatidylcholine (PC), phosphatidylethanolamine (PE),
triacylglycerol (TG) and lysophosphatidylcholine (lysoPC). Data are means+SD (n ¼ 3).
The zebrafish system can be used to screen angiogenic drugs (Chan et al.,
2002) – compounds that affect embryogenesis (Peterson et al., 2000) – and is