INHIBITION OF FATTY ACID DESATURASES IN Drosophila melanogaster LARVAE BLOCKS FEEDING AND DEVELOPMENTAL PROGRESSION

Abstract

Fatty acid desaturases are metabolic setscrews. To study their systemic impact on growth in Drosophila melanogaster, we inhibited fatty acid desaturases using the inhibitor CAY10566. As expected, the amount of desaturated lipids is reduced in larvae fed with CAY10566. These animals cease feeding soon after hatching, and their growth is strongly attenuated. A starvation program is not launched, but the expression of distinct metabolic genes is activated, possibly to mobilize storage material. Without attaining the normal size, inhibitor-fed larvae molt to the next stage indicating that the steroid hormone ecdysone triggers molting correctly. Nevertheless, after molting, expression of ecdysone-dependent regulators is not induced. While control larvae molt a second time, these larvae fail to do so and die after few days of straying. These effects are similar to those observed in experiments using larvae deficient for the fatty acid desaturase1 gene. Based on these data, we propose that the ratio of saturated to unsaturated fatty acids adjusts a sensor system that directs feeding behavior. We also hypothesize that loss of fatty acid desaturase activity leads to a block of the genetic program of development progression indirectly by switching on a metabolic compensation program.

Inhibition of fatty acid desaturation impairs cuticle differentiation in Drosophila melanogaster

“…In a previous work, we showed that the profile of cuticular hydrocarbons (CHC) is changed in larvae with inhibited fatty acid desaturation (Wang et al, ). To learn about the impact of fatty acid desaturation by Desats on lipid distribution in the cuticle, we imaged lipids in live animals fed with Bodipy 505/515 and the Desat inhibitor CAY10566 by confocal microscopy (Figure ).…”

“…By contrast, Desat1 is essential for viability. It is expressed at all stages and is among others involved in the synthesis of desaturated CHCs (Ferveur et al, ; Wang et al, ). Interestingly, the cuticle barrier efficiency depends on the ratio of desaturated to saturated CHCs, rather than on the total amounts of desaturated CHC.…”

“…Day 2 larvae were analysed after an additional day (39–42 hr) of feeding, again around the time of the 20HE peak (Lavrynenko et al, ). Of note, we have never obtained third instar larvae after CAY10566 feeding of first instar larvae (Wang et al, ) that would have allowed more detailed analyses. Control larvae were fed with yeast containing the same amount of DMSO (8 μl).…”

“…Besides these intrinsic programs, nutrition plays an important role in development control (Koyama, Rodrigues, Athanasiadis, Shingleton, & Mirth, ). Previously, we showed that inhibition of fatty desaturase activity in D. melanogaster larvae perturbs 20HE signalling and tunes the expression of the metabolic gene (Wang et al, ). As a consequence, these larvae were unable to moult to the next stage.…”

“…Lipid degradation is attenuated and sugar metabolism is enhanced in desat‐inhibited larvae. We proposed that the ratio between saturated and desaturated fatty acids might serve as a sensor that controls the behaviour of the larva (Wang et al, ). Here, we present our data on the effects of desat deactivation on cuticle differentiation.…”