Metabolic and transcriptional response to a high-fat diet in Drosophila melanogaster.
Metabolic and transcriptional response to a high-fat diet in Drosophila melanogaster.
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DOI：
10.1016/j.molmet.2013.10.003
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发表时间：
2014-02
影响因子：
8.1
通讯作者：
Haddad GG
中科院分区：
文献类型：
--
作者：
Heinrichsen ET;Zhang H;Robinson JE;Ngo J;Diop S;Bodmer R;Joiner WJ;Metallo CM;Haddad GG
肥胖症的患病率急剧增加，因此了解其伴随的代谢变化至关重要。在果蝇（果蝇）中建立饮食诱导的肥胖模型，我们阐明了高脂饮食（HFD）中w1118果蝇的转录和代谢变化。基于质谱的代谢组学显示HFD改变了脂肪酸、氨基酸和碳水化合物代谢。微阵列分析揭示了氮代谢中的转录变化，包括CG9510，人氨基琥珀酸裂解酶（ASL）的同系物。在果蝇中的CG9510敲除与用HFD观察到的性状表型相似，即增加的甘油三酯水平和降低的耐冷性。CG9510表达的恢复改善了观察到的HFD的负面后果。CG9510基因敲除果蝇的代谢组学分析证实了与ASL的功能相似，调节碳和氮代谢的平衡。总之，我们发现HFD抑制CG9510表达，CG9510是适当的甘油三酯储存和应激耐受所需的基因。这些结果在氨基酸代谢的调节和对饮食诱导的肥胖的反应之间建立了重要联系。
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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DOI：
10.1073/pnas.0702726104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Ja, William W.;Carvalho, Gil B.;Benzer, Seymour
通讯作者：
Benzer, Seymour
影响因子：
120.7
作者：
Hedley, AA;Ogden, CL;Flegal, KM
通讯作者：
Flegal, KM
影响因子：
120.7
作者：
Fontaine, KR;Redden, DT;Allison, DB
通讯作者：
Allison, DB
影响因子：
4.2
作者：
Layman, DK;Walker, DA
通讯作者：
Walker, DA
影响因子：
29
作者：
Birse RT;Choi J;Reardon K;Rodriguez J;Graham S;Diop S;Ocorr K;Bodmer R;Oldham S
通讯作者：
Oldham S