Metabolic and Transcriptional Response to a High-fat Diet in Drosophila Melanogaster

Overview

Journal Mol Metab

Specialty Cell Biology

Date 2014 Feb 26

PMID 24567903

Citations 54

Authors

Erilynn T Heinrichsen

Hui Zhang

James E Robinson

John Ngo

Soda Diop

Rolf Bodmer

William J Joiner

Christian M Metallo

Gabriel G Haddad

Affiliations

Soon will be listed here.

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.

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