We have previously identified several N-acylethanolamines (NAEs) in C. elegans and found that they are important for development and influence adult lifespan. In mammals, the activity of NAEs is regulated by the relative activity of the biosynthetic enzyme N-acyl phosphatidylethanolamine (NAPE-PLD) and the hydrolytic enzyme fatty acid amide hydrolase (FAAH). Here we focus on the two C. elegans NAPE-PLD homologs,
nape-1 and
nape-2, and characterize their roles in NAE biosynthesis as well as their effects on life history traits. Although these enzymes have strong sequence similarity, and are expressed in overlapping tissues, they are also expressed in discrete areas suggesting the possibility of divergent functions. We find that they are both capable of liberating NAEs from N-acyl phosphatidylethanolamine substrates in vitro and over-expression of each enzyme increases NAE levels in vivo. Surprisingly, this effect is temperature-dependent, with
nape-1 being most effective at 25 deg C and
nape-2 at 15 deg C. These alterations in NAE levels are reflected in temperature-dependent differences in phenotypes.
nape-1 over-expressers have growth delay and shortened lifespan at 25 deg C, but not at 15 deg C. In contrast,
nape-2 over-expression results in a significant fraction of L1 arrest at 15 deg C but extends adult lifespan in those animals that do not arrest.
nape-1 over-expressers show decreased satiety quiescence in both the unfasted state and during refeeding after fasting, but
nape-2 over-expression has no apparent effect on satiety quiescence. Interestingly, when the nape over-expressers are crossed into a
faah-1 deletion mutant, the growth phenotype of
nape-1 is exacerbated, as expected, but the L1 arrest associated with
nape-2 is fully rescued. In summary, these results provide evidence for a conservation of NAE metabolism between C. elegans and mammals, and indicate that
nape-1 and
nape-2 have different roles in mediating temperature-dependent effects of NAEs.