Deficiencies in acetyl-CoA carboxylase and fatty acid synthase 1 differentially affect eggshell formation and blood meal digestion in Aedes aegypti.
Deficiencies in acetyl-CoA carboxylase and fatty acid synthase 1 differentially affect eggshell formation and blood meal digestion in Aedes aegypti.
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DOI：
10.1016/j.ibmb.2011.09.004
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发表时间：
2011-12
影响因子：
3.8
通讯作者：
Miesfeld, Roger L.
中科院分区：
文献类型：
--
作者：
Alabaster, Amy;Isoe, Jun;Zhou, Guoli;Lee, Ada;Murphy, Ashleigh;Day, W. Anthony;Miesfeld, Roger L.
为了更好地了解喂饲Ae的血液中从头合成脂质的机制。以埃及伊蚊为研究对象，我们定量检测了采血蚊体中乙酰-辅酶A羧基酶(ACC)和脂肪酸合成酶1(FAS1)的转录水平，并利用RNAi方法产生了ACC和FAS1缺陷的蚊子。以生酮氨基酸14C-亮氨酸作为14C-乙酰-辅酶A的代谢前体，我们发现在ACC和FAS1缺陷的蚊子中，14C-三酰甘油和14C-磷脂的水平都显著降低，证实了ACC和FAS1是采血后从头合成脂肪所必需的。然而，令人惊讶的是，我们还发现，缺乏ACC的蚊子，而不是FAS1缺乏的蚊子，会产生有缺陷的卵母细胞，这些有缺陷的卵子缺乏完整的蛋壳，从而产生无法存活的卵子。这种严重的表型仅限于第一个性腺营养周期，这表明蛋壳缺陷是由于滤泡上皮细胞中ACC缺乏所致，在每个性腺营养周期后，这些细胞被替换。在第1个和第2个生殖营养周期中，ACC和FAS1缺陷蚊子的产卵量明显少于对照蚊子，这与从头合成脂肪的量较少一致。最后，缺乏FAS1的蚊子，而不是缺乏ACC的蚊子，表现出延迟的血粉消化，这表明反馈控制机制可能协调了摄食过程中脂肪体脂肪生物合成和中肠消化的速度。我们认为，ACC和FAS1酶水平的降低导致脂肪生物合成减少和繁殖力下降，而调节代谢物乙酰辅酶A和丙二酰辅酶A的水平变化分别解释了观察到的蛋壳形成和血粉消化的缺陷。
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.
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