Metabolism and development must be closely coupled to meet the changing physiological needs of each stage in the life cycle. The molecular mechanisms that link these pathways, however, remain poorly understood. Here we show that the Drosophila estrogen-related receptor (dERR) directs a transcriptional switch in mid-pupae that promotes glucose oxidation and lipogenesis in young adults. dERR mutant adults are viable but display reduced locomotor activity, susceptibility to starvation, elevated glucose, and an almost complete lack of stored triglycerides. Molecular profiling by RNA-seq, ChIP-seq, and metabolomics revealed that glycolytic and pentose phosphate pathway genes are induced by dERR, and their reduced expression in mutants is accompanied by elevated glycolytic intermediates, reduced TCA cycle intermediates, and reduced levels of long chain fatty acids. Unexpectedly, we found that the central pathways of energy metabolism, including glycolysis, the tricarboxylic acid cycle, and electron transport chain, are coordinately induced at the transcriptional level in mid-pupae and maintained into adulthood, and this response is partially dependent on dERR, leading to the metabolic defects observed in mutants. Our data support the model that dERR contributes to a transcriptional switch during pupal development that establishes the metabolic state of the adult fly.

中文翻译：

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果蝇雌激素相关受体指导支持成人糖酵​​解和脂肪生成的转录开关。

新陈代谢和发育必须紧密结合，以满足生命周期中每个阶段不断变化的生理需求。然而，连接这些途径的分子机制仍然知之甚少。在这里，我们表明果蝇雌激素相关受体 (dERR) 指导中蛹的转录开关，促进年轻成人的葡萄糖氧化和脂肪生成。dERR 突变体成体是可行的，但表现出运动活性降低、对饥饿的易感性、葡萄糖升高以及几乎完全缺乏储存的甘油三酯。通过 RNA-seq、ChIP-seq 和代谢组学进行的分子谱分析表明，糖酵解和磷酸戊糖途径基因是由 dERR 诱导的，它们在突变体中的表达减少伴随着糖酵解中间体的升高、TCA 循环中间体的减少，并减少长链脂肪酸的含量。出乎意料的是，我们发现能量代谢的中枢途径，包括糖酵解、三羧酸循环和电子传递链，在中蛹的转录水平上被协调诱导并维持到成年期，这种反应部分依赖于 dERR，导致在突变体中观察到的代谢缺陷。我们的数据支持 dERR 在蛹发育过程中促进转录转换的模型，该转换建立了成年果蝇的代谢状态。并且这种反应部分依赖于 dERR，导致在突变体中观察到的代谢缺陷。我们的数据支持 dERR 在蛹发育过程中促进转录转换的模型，该转换建立了成年果蝇的代谢状态。并且这种反应部分依赖于 dERR，导致在突变体中观察到的代谢缺陷。我们的数据支持 dERR 在蛹发育过程中促进转录转换的模型，该转换建立了成年果蝇的代谢状态。