Endocannabinoids in Caenorhabditis elegans are essential for the mobilization of cholesterol from internal reserves
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Proper cholesterol transport is crucial for the functionality of cells. In C. elegans, certain cholesterol
derivatives called dafachronic acids (DAs) govern the entry into diapause. In their absence, worms
form a developmentally arrested dauer larva. Thus, cholesterol transport to appropriate places
for DA biosynthesis warrants the reproductive growth. Recently, we discovered a novel class of
glycosphingolipids, PEGCs, required for cholesterol mobilization/transport from internal storage
pools. Here, we identify other components involved in this process. We found that strains lacking
polyunsaturated fatty acids (PUFAs) undergo increased dauer arrest when grown without cholesterol.
This correlates with the depletion of the PUFA-derived endocannabinoids 2-arachidonoyl glycerol and
anandamide. Feeding of these endocannabinoids inhibits dauer formation caused by PUFAs defciency
or impaired cholesterol trafcking (e.g. in Niemann-Pick C1 or DAF-7/TGF-β mutants). Moreover, in
parallel to PEGCs, endocannabinoids abolish the arrest induced by cholesterol depletion. These fndings
reveal an unsuspected function of endocannabinoids in cholesterol trafcking regulation.
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