Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
Vital-IT, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
J Clin Invest. 2023 Apr 17;133(8):e167133. doi: 10.1172/JCI167133.
Circadian rhythmicity in renal function suggests rhythmic adaptations in renal metabolism. To decipher the role of the circadian clock in renal metabolism, we studied diurnal changes in renal metabolic pathways using integrated transcriptomic, proteomic, and metabolomic analysis performed on control mice and mice with an inducible deletion of the circadian clock regulator Bmal1 in the renal tubule (cKOt). With this unique resource, we demonstrated that approximately 30% of RNAs, approximately 20% of proteins, and approximately 20% of metabolites are rhythmic in the kidneys of control mice. Several key metabolic pathways, including NAD+ biosynthesis, fatty acid transport, carnitine shuttle, and β-oxidation, displayed impairments in kidneys of cKOt mice, resulting in perturbed mitochondrial activity. Carnitine reabsorption from primary urine was one of the most affected processes with an approximately 50% reduction in plasma carnitine levels and a parallel systemic decrease in tissue carnitine content. This suggests that the circadian clock in the renal tubule controls both kidney and systemic physiology.
肾功能的昼夜节律表明肾脏代谢存在节律适应性。为了解析生物钟在肾脏代谢中的作用，我们使用整合的转录组学、蛋白质组学和代谢组学分析方法，研究了对照小鼠和在肾小管中诱导敲除生物钟调节因子 Bmal1 的小鼠（cKOt）的昼夜变化。利用这一独特的资源，我们证明了大约 30%的 RNA、大约 20%的蛋白质和约 20%的代谢物在对照小鼠的肾脏中呈现节律性。几种关键的代谢途径，包括 NAD+生物合成、脂肪酸转运、肉碱穿梭和β-氧化，在 cKOt 小鼠的肾脏中显示出损伤，导致线粒体活性紊乱。初级尿液中的肉碱重吸收是受影响最严重的过程之一，血浆肉碱水平下降约 50%，组织肉碱含量呈平行性系统下降。这表明肾脏小管中的生物钟控制着肾脏和全身的生理机能。
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