Gao Xinsheng, Xie Xiao-Jun, Hsu Fu-Ning, Li Xiao, Liu Mengmeng, Hemba-Waduge Rajitha-Udakara-Sampath, Xu Wu, Ji Jun-Yuan
Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA.
Department of Chemistry, University of Louisiana at Lafayette, Lafayette, LA 70504, USA.
Dev Biol. 2018 Dec 15;444(2):62-70. doi: 10.1016/j.ydbio.2018.10.001. Epub 2018 Oct 21.
The complex interplay between genetic and environmental factors, such as diet and lifestyle, defines the initiation and progression of multifactorial diseases, including cancer, cardiovascular and metabolic diseases, and neurological disorders. Given that most of the studies have been performed in controlled experimental settings to ensure the consistency and reproducibility, the impacts of environmental factors, such as dietary perturbation, on the development of animals with different genotypes and the pathogenesis of these diseases remain poorly understood. By analyzing the cdk8 and cyclin C (cycC) mutant larvae in Drosophila, we have previously reported that the CDK8-CycC complex coordinately regulates lipogenesis by repressing dSREBP (sterol regulatory element-binding protein)-activated transcription and developmental timing by activating EcR (ecdysone receptor)-dependent gene expression. Here we report that dietary nutrients, particularly proteins and carbohydrates, modulate the developmental timing through the CDK8/CycC/EcR pathway. We observed that cdk8 and cycC mutants are sensitive to the levels of dietary proteins and seven amino acids (arginine, glutamine, isoleucine, leucine, methionine, threonine, and valine). Those mutants are also sensitive to dietary carbohydrates, and they are more sensitive to monosaccharides than disaccharides. These results suggest that CDK8-CycC mediates the dietary effects on lipid metabolism and developmental timing in Drosophila larvae.
遗传因素与环境因素(如饮食和生活方式)之间复杂的相互作用,决定了包括癌症、心血管疾病、代谢性疾病和神经紊乱在内的多因素疾病的发生和发展。鉴于大多数研究是在可控的实验环境中进行的,以确保一致性和可重复性,环境因素(如饮食扰动)对不同基因型动物发育以及这些疾病发病机制的影响仍知之甚少。通过分析果蝇中的cdk8和细胞周期蛋白C(cycC)突变幼虫,我们之前报道过CDK8 - CycC复合物通过抑制dSREBP(固醇调节元件结合蛋白)激活的转录来协调调节脂肪生成,并通过激活EcR(蜕皮激素受体)依赖性基因表达来调节发育时间。在此我们报道,饮食营养物质,特别是蛋白质和碳水化合物,通过CDK8/CycC/EcR途径调节发育时间。我们观察到cdk8和cycC突变体对饮食蛋白质水平以及七种氨基酸(精氨酸、谷氨酰胺、异亮氨酸、亮氨酸、蛋氨酸、苏氨酸和缬氨酸)敏感。这些突变体对饮食碳水化合物也敏感,并且它们对单糖比对双糖更敏感。这些结果表明CDK8 - CycC介导了饮食对果蝇幼虫脂质代谢和发育时间的影响。
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