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Metabolic and transcriptional response to a high-fat diet in Drosophila melanogaster

Authors
  • Heinrichsen, Erilynn T.
  • Zhang, Hui
  • Robinson, James E.
  • Ngo, John
  • Diop, Soda
  • Bodmer, Rolf
  • Joiner, William J.
  • Metallo, Christian M.
  • Haddad, Gabriel G.1, 2, 3, 4, 5, 6, 7
  • 1 Department of Pediatrics (Division of Respiratory Medicine), University of California
  • 2 Department of Bioengineering, University of California
  • 3 Department of Neurosciences, University of California
  • 4 Department of Pharmacology, University of California
  • 5 Biomedical Sciences Graduate Program, University of California
  • 6 Development and Aging Program, NASCR Center, Sanford/Burnham Medical Research Institute
  • 7 Rady Children's Hospital
Type
Published Article
Journal
Molecular Metabolism
Publisher
Elsevier BV
Publication Date
Jan 01, 2013
Accepted Date
Oct 17, 2013
Volume
3
Issue
1
Pages
42–54
Identifiers
DOI: 10.3791/1425
Source
Elsevier
Keywords
License
Unknown

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.

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