Deficiencies in acetyl-CoA carboxylase and fatty acid synthase 1 differentially affect eggshell formation and blood meal digestion in Aedes aegypti

Abstract

To better understand the mechanism of de novo lipid biosynthesis in blood fed Ae. aegypti mosquitoes, we quantitated acetyl-CoA carboxylase (ACC) and fatty acid synthase 1 (FAS1) transcript levels in blood fed mosquitoes, and used RNAi methods to generate ACC and FAS1 deficient mosquitoes. Using the ketogenic amino acid 14C-leucine as a metabolic precursor of 14C-acetyl-CoA, we found that 14C-triacylglycerol and 14C-phospholipid levels were significantly reduced in both ACC and FAS1 deficient mosquitoes, confirming that ACC and FAS1 are required for de novo lipid biosynthesis after blood feeding. Surprisingly however, we also found that ACC deficient mosquitoes, but not FAS1 deficient mosquitoes, produced defective oocytes, which lacked an intact eggshell and gave rise to inviable eggs. This severe phenotype was restricted to the 1st gonotrophic cycle, suggesting that the eggshell defect was due to ACC deficiencies in the follicular epithelial cells, which are replaced after each gonotrophic cycle. Consistent with lower amounts of de novo lipid biosynthesis, both ACC and FAS1 deficient mosquitoes produced significantly fewer eggs than control mosquitoes in both the 1st and 2nd gonotrophic cycles. Lastly, FAS1 deficient mosquitoes, but not ACC deficient mosquitoes, showed delayed blood meal digestion, suggesting that a feedback control mechanism may coordinate rates of fat body lipid biosynthesis and midgut digestion during feeding. We propose that decreased ACC and FAS1 enzyme levels lead to reduced lipid biosynthesis and lower fecundity, whereas altered levels of the regulatory metabolites acetyl-CoA and malonyl-CoA account for the observed defects in eggshell formation and blood meal digestion, respectively.

De Novo Biosynthesis of Sexual Pheromone in the Labial Gland of Bumblebee Males

“…B. terrestris FAS (GenBank accession number: JN982132) shares 96 % sequence identity with the predicted FAS from Bombus impatiens, 75 % identity with the predicted FAS from A. mellifera, and 55 % identity with a previously characterized FAS from Aedes aegypti. [41] We detected an increasing level of B. terrestris FAS transcripts in LG from pharate imago up to three days old. There was a modest decrease in LG FAS transcript level in five-day-old bumblebees.…”

Spirotetramat resistance adaption analysis of Aphis gossypii Glover by transcriptomic survey

“…ACC-deficient mosquitoes produce defective oocytes that lack intact eggshells and give rise to nonviable eggs [24]. One explanation for the observed defect in eggshell formation in ACCdeficient mosquitoes is that de novo fatty acid biosynthesis in ovary tissues is required to generate the lipid components of the eggshell [25].…”

Fatty acid synthase 2 contributes to diapause preparation in a beetle by regulating lipid accumulation and stress tolerance genes expression

“…It has been demonstrated that fatty acid synthase (FAS) plays a central role in lipid accumulation in both vertebrates and invertebrates91011. FAS regulates de novo lipogenesis by converting acetyl-CoA into palmitate, leading to the production and storage of triacylglyceride (TG)12.…”

“…Upregulation of FAS was observed during early diapause in the mosquito Culex pipiens 1314 and knockdown of FAS1 reduced lipid accumulation and affected the overwintering survival of females of this species15. FAS has also been found to promote lipid accumulation in another mosquito Aedes aegypti 9. It is now generally accepted that FAS regulates lipid accumulation in insect diapause.…”