title: Metabolic and transcriptional response to a high-fat diet in Drosophila melanogaster.
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 w (1118) 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.
authors.affiliation: Department of Pediatrics (Division of Respiratory Medicine), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA ; Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Erilynn T
authors.initials: ET
authors.lastname: Heinrichsen
authors.affiliation: Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA ; Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
authors.affiliation: Department of Pediatrics (Division of Respiratory Medicine), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: John
authors.initials: J
authors.lastname: Ngo
authors.affiliation: Development and Aging Program, NASCR Center, Sanford/Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Soda
authors.initials: S
authors.lastname: Diop
authors.affiliation: Development and Aging Program, NASCR Center, Sanford/Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
authors.affiliation: Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA ; Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Joiner
authors.affiliation: Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Metallo
authors.affiliation: Department of Pediatrics (Division of Respiratory Medicine), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA ; Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA ; Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA ; Rady Children's Hospital, 3020 Children's Way, San Diego, CA 92123, USA.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Haddad
keywords: ASL, argininosuccinate lyase; AcCoA, acetyl-coenzyme A; Argininosuccinate lyase; BCAA, branch chain amino acid; CAFE, capillary feeder; EASE, Expression Analysis Systematic Explorer (DAVID analysis); FAME, fatty acid methyl ester; Fdr, false discovery rate; GC/MS, gas chromatography/mass spectrometry; HFD, high-fat Diet; Lifespan; MeOH, methanol; Metabolism; Obesity; PCR, polymerase chain reaction; RT-PCR, reverse-transcriptase PCR; TBDMS, tert-butyldimethylsilyl; TCA, tricarboxylic acid; TG, triglyceride; TMS, trimethylsilyl; Triglyceride; VDRC, Vienna Drosophila RNAi Center; arm-GAL4, armadillo-GAL4; da-GAL4, daughterless-Gal4; w1118, white-1118