A whole-animal phenotypic drug screen identifies suppressors of atherogenic lipoproteins
Lipoproteins are essential for lipid transport in all bilaterians. A single Apolipoprotein B (ApoB) molecule is the inseparable structural scaffold of each ApoB-containing lipoprotein (B-lps), which are responsible for transporting lipids to peripheral tissues. The cellular mechanisms that regulate ApoB and B-lp production, secretion, transport, and degradation remain to be fully defined. In…
A comprehensive study screened nearly 3000 compounds in zebrafish, yielding 49 compounds that effectively lower Apolipoprotein B (ApoB)-containing lipoproteins (B-lps). After rigorous testing, seven compounds were chosen for further phenotypic examination. Among these, enoxolone, derived from licorice root, demonstrated a significant reduction in B-lp levels, but only in zebrafish with fully functional Hepatocyte Nuclear Factor 4α (HNF4α) genes.
Similarly, inhibitors of HNF4α also lowered B-lp levels. These findings highlight the effectiveness of a whole-animal zebrafish phenotypic screen in swiftly determining the mechanism of action for B-lp lowering compounds. The results strongly support the LipoGlo screening platform as a valuable tool for discovering small-molecule modulators of B-lps, which are crucial players in cardiovascular disease, a leading cause of global mortality.
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