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.
Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Mol Metab. 2013 Oct 23;3(1):42-54. doi: 10.1016/j.molmet.2013.10.003. eCollection 2014 Feb.
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.
肥胖症的患病率显著增加，因此了解其伴随的代谢变化至关重要。我们通过在果蝇（黑腹果蝇）中模拟饮食诱导的肥胖症，阐明了高脂肪饮食（HFD）下 w（1118）果蝇的转录和代谢变化。基于质谱的代谢组学分析显示，HFD 导致脂肪酸、氨基酸和碳水化合物代谢发生改变。微阵列分析揭示了氮代谢的转录变化，包括 CG9510，人类精氨琥珀酸裂解酶（ASL）的同源物。果蝇中 CG9510 的敲低表现出与 HFD 观察到的特征相似，即甘油三酯水平升高和耐寒性降低。CG9510 表达的恢复改善了 HFD 观察到的负面影响。CG9510 敲低果蝇的代谢组学分析证实了与 ASL 的功能相似性，调节碳氮代谢的平衡。总之，我们发现 HFD 抑制了 CG9510 的表达，该基因对于正常的甘油三酯储存和应激耐受是必需的。这些结果在调节氨基酸代谢和对饮食诱导的肥胖症的反应之间建立了重要联系。
