1. Metabolic and transcriptional response to a high-fat diet in Drosophila melanogaster
- Author
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William J. Joiner, John T. Ngo, Christian M. Metallo, Rolf Bodmer, Hui Zhang, Soda Balla Diop, Gabriel G. Haddad, Erilynn T. Heinrichsen, and James E. Robinson
- Subjects
EASE, Expression Analysis Systematic Explorer (DAVID analysis) ,Physiology ,polymerase chain reaction ,capillary feeder ,BCAA, branch chain amino acid ,w1118 ,AcCoA, acetyl-coenzyme A ,da-GAL4 ,Triglyceride ,TMS, trimethylsilyl ,Argininosuccinate lyase ,chemistry.chemical_compound ,PCR, polymerase chain reaction ,VDRC, Vienna Drosophila RNAi Center ,acetyl-coenzyme A ,CAFE ,branch chain amino acid ,BCAA ,high-fat Diet ,chemistry.chemical_classification ,Gene knockdown ,TG, triglyceride ,biology ,Lifespan ,TBDMS, tert-butyldimethylsilyl ,GC/MS ,fatty acid methyl ester ,TCA ,ASL, argininosuccinate lyase ,GC/MS, gas chromatography/mass spectrometry ,Cell biology ,Expression Analysis Systematic Explorer ,Vienna Drosophila RNAi Center ,white-1118 ,PCR ,HFD, high-fat Diet ,Biochemistry ,arm-GAL4, armadillo-GAL4 ,Original Article ,TG ,arm-GAL4 ,Drosophila melanogaster ,CAFE, capillary feeder ,EASE ,TCA, tricarboxylic acid ,RT-PCR ,tert-butyldimethylsilyl ,Carbohydrate metabolism ,Fdr ,gas chromatography/mass spectrometry ,Metabolomics ,VDRC ,ASL ,armadillo-GAL4 ,Obesity ,Molecular Biology ,Metabolic and endocrine ,methanol ,Nutrition ,w1118, white-1118 ,Prevention ,FAME, fatty acid methyl ester ,Fatty acid ,trimethylsilyl ,Cell Biology ,Metabolism ,reverse-transcriptase PCR ,biology.organism_classification ,MeOH ,FAME ,chemistry ,daughterless-Gal4 ,da-GAL4, daughterless-Gal4 ,RT-PCR, reverse-transcriptase PCR ,TMS ,Fdr, false discovery rate ,HFD ,AcCoA ,false discovery rate ,Biochemistry and Cell Biology ,MeOH, methanol ,TBDMS ,tricarboxylic acid - Abstract
Obesity has dramatically increased in prevalence, making it essential to understand its accompanying metabolic changes. Modeling diet-induced obesity in Drosophila melanogaster (fruit flies), we elucidated transcriptional and metabolic changes in w1118 flies on a high-fat diet (HFD). Mass spectrometry-based metabolomics revealed altered fatty acid, amino acid, and carbohydrate metabolism with HFD. Microarray analysis uncovered transcriptional changes in nitrogen metabolism, including CG9510, homolog of human argininosuccinate lyase (ASL). CG9510 knockdown in flies phenocopied traits observed with HFD, namely increased triglyceride levels and decreased cold tolerance. Restoration of CG9510 expression ameliorated observed negative consequences of HFD. Metabolomic analysis of CG9510 knockdown flies confirmed functional similarity to ASL, regulating the balance of carbon and nitrogen metabolism. In summary, we found that HFD suppresses CG9510 expression, a gene required for proper triglyceride storage and stress tolerance. These results draw an important link between regulation of amino acid metabolism and the response to diet-induced obesity. © 2013 The Authors.
- Published
- 2014
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