State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):E2709-E2718. doi: 10.1073/pnas.1619326114. Epub 2017 Mar 14.
Mosquitoes transmit devastating human diseases because they need vertebrate blood for egg development. Metabolism in female mosquitoes is tightly coupled with blood meal-mediated reproduction, which requires an extremely high level of energy consumption. Functional analysis has shown that major genes encoding for enzymes involved in lipid metabolism (LM) in the mosquito fat bodies are down-regulated at the end of the juvenile hormone (JH)-controlled posteclosion (PE) phase but exhibit significant elevation in their transcript levels during the post-blood meal phase (PBM), which is regulated mainly by 20-hydroxyecdysone (20E). Reductions in the transcript levels of genes encoding triacylglycerol (TAG) catabolism and β-oxidation enzymes were observed to correlate with a dramatic accumulation of lipids in the PE phase; in contrast, these transcripts were elevated significantly and lipid stores were diminished during the PBM phase. The RNAi depletion of Methoprene-tolerant (Met) and ecdysone receptor (EcR), receptors for JH and 20E, respectively, reversed the LM gene expression and the levels of lipid stores and metabolites, demonstrating the critical roles of these hormones in LM regulation. Hepatocyte nuclear factor 4 (HNF4) RNAi-silenced mosquitoes exhibited down-regulation of the gene transcripts encoding TAG catabolism and β-oxidation enzymes and an inability to use lipids effectively, as manifested by TAG accumulation. The luciferase reporter assay showed direct regulation of LM-related genes by HNF4. Moreover, gene expression was down-regulated by Met and activated by EcR and Target of rapamycin, providing a link between nutritional and hormonal regulation of LM in female mosquitoes.
蚊子传播破坏性的人类疾病，因为它们的卵发育需要脊椎动物的血液。雌性蚊子的新陈代谢与血餐介导的繁殖紧密耦合，这需要极高的能量消耗。功能分析表明，蚊子脂肪体中参与脂质代谢 (LM) 的主要基因编码的酶在保幼激素 (JH) 控制的后期胚胎发生 (PE) 阶段结束时下调，但在血餐后阶段 (PBM) 其转录水平显著升高，这主要受 20-羟基蜕皮酮 (20E) 调节。观察到编码三酰基甘油 (TAG) 分解和β-氧化酶的基因转录水平降低与 PE 阶段脂质的剧烈积累相关；相比之下，这些转录物在 PBM 阶段显著升高，脂质储存减少。Methoprene-tolerant (Met) 和蜕皮激素受体 (EcR) 的 RNAi 耗尽，分别是 JH 和 20E 的受体，逆转了 LM 基因表达和脂质储存和代谢物水平，表明这些激素在 LM 调节中的关键作用。肝细胞核因子 4 (HNF4) 的 RNAi 沉默蚊子表现出 TAG 分解和β-氧化酶基因转录物的下调，以及不能有效地利用脂质，表现为 TAG 积累。荧光素酶报告基因检测表明 HNF4 直接调节 LM 相关基因。此外，基因表达被 Met 下调，被 EcR 和雷帕霉素靶蛋白激活，为雌性蚊子的营养和激素调节提供了联系。
