Document Detail

Deficiencies in acetyl-CoA carboxylase and fatty acid synthase 1 differentially affect eggshell formation and blood meal digestion in Aedes aegypti.
MedLine Citation:
PMID:  21971482     Owner:  NLM     Status:  MEDLINE    
To better understand the mechanism of de novo lipid biosynthesis in blood fed Aedes 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 (14)C-leucine as a metabolic precursor of (14)C-acetyl-CoA, we found that (14)C-triacylglycerol and (14)C-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.
Amy Alabaster; Jun Isoe; Guoli Zhou; Ada Lee; Ashleigh Murphy; W Anthony Day; Roger L Miesfeld
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-29
Journal Detail:
Title:  Insect biochemistry and molecular biology     Volume:  41     ISSN:  1879-0240     ISO Abbreviation:  Insect Biochem. Mol. Biol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-07     Completed Date:  2012-02-07     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  9207282     Medline TA:  Insect Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  946-55     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Acetyl-CoA Carboxylase / genetics,  metabolism*
Aedes / enzymology*,  genetics
Blood / metabolism
Fat Body / metabolism
Fatty Acid Synthases / genetics,  metabolism*
Insect Proteins / genetics,  metabolism*
Lipid Metabolism*
Ovum / physiology*
Grant Support
R01 AI031951/AI/NIAID NIH HHS; R01 AI031951-17/AI/NIAID NIH HHS; R01 AI031951-17S1/AI/NIAID NIH HHS; R01 AI031951-18/AI/NIAID NIH HHS; R01 AI046541/AI/NIAID NIH HHS; R01 AI046541-09/AI/NIAID NIH HHS; R01 AI046541-09S1/AI/NIAID NIH HHS; R01 AI046541-10/AI/NIAID NIH HHS; R01AI046451/AI/NIAID NIH HHS
Reg. No./Substance:
0/Insect Proteins; EC Acid Synthases; EC Carboxylase

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