Developmental ethanol exposure leads to dysregulation of lipid metabolism and oxidative stress in Drosophila.
Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD.
Department of Biological Sciences, San José State University, 1 Washington Square, San José, California 95192-0100.
Theresa
T
Logan-Garbisch
Department of Biological Sciences, San José State University, 1 Washington Square, San José, California 95192-0100.
Anthony
A
Bortolazzo
Department of Biological Sciences, San José State University, 1 Washington Square, San José, California 95192-0100.
Peter
P
Luu
Department of Biological Sciences, San José State University, 1 Washington Square, San José, California 95192-0100.
Audrey
A
Ford
Department of Biological Sciences, San José State University, 1 Washington Square, San José, California 95192-0100.
David
D
Do
Department of Biological Sciences, San José State University, 1 Washington Square, San José, California 95192-0100.
Payam
P
Khodabakhshi
Department of Biological Sciences, San José State University, 1 Washington Square, San José, California 95192-0100 rachael.french@sjsu.edu.
Rachael L
RL
French
D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress
D029721:Drosophila Proteins; D000431:Ethanol; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578560:Pdk1 protein, Drosophila
carnitine transporter; fetal alcohol syndrome; lipid accumulation; reactive oxygen species; withered