Circadian period of luciferase expression shortens with age in human mature adipocytes from obese patients.
Circadian period of luciferase expression shortens with age in human mature adipocytes from obese patients.
复制标题
在肥胖患者的人类成熟脂肪细胞中，荧光素酶表达的昼夜节律随着年龄的增长而缩短。
DOI：
10.1096/fj.201800441r
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Garaulet,Marta
中科院分区：
文献类型：
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作者：
Kolbe,Isa;Carrasco-Benso,MaríaPaz;López-Mínguez,Jesús;Luján,Juan;Scheer,FrankAJL;Oster,Henrik;Garaulet,Marta
生理和行为的日常节律随着年龄的增长而变化。一个尚未解决的问题是，这种与年龄相关的昼夜节律组织变化在多大程度上是由视交叉上核（SCN）中的中央时钟驱动的，修改了贡献外周组织振荡器的定时信号，并由局部细胞振荡器本身的潜在变化介导。使用生物发光报告方法，我们试图确定来自皮下（SAT）和内脏（VAT）脂肪组织的人脂肪细胞的生物钟功能是否随年龄变化。在胃旁路手术期间从肥胖个体中获得SAT和VAT活检[n = 16;体重指数：44.8 ± 11.4 kg/m2;年龄：44 ± 9岁（范围：30-58）]。分离细胞并用慢病毒昼夜节律报告基因构建体[脑和肌肉芳烃受体核转位样：荧光素酶（BMAL：LUC）]转导，并在3天的时间内记录生物发光。人BMAL 1：LUC脂肪细胞显示出稳定的发光节律，成熟脂肪细胞和前脂肪细胞的个体内周期相当（P > 0.05）。随着年龄的增长，成熟脂肪细胞的昼夜节律周期缩短（P = 0.005）（β = 4 min/yr; P < 0.05）。我们的离体方法表明，衰老会改变人类脂肪细胞中内源性昼夜节律振荡器的组织，而与SCN信号传导无关。科尔贝岛Carrasco-Benso，M. P.，López-Mínguez，J.，Luján，J.，Scheer，F. A. J. L.，奥斯特，H.，加劳莱特湾肥胖患者成熟脂肪细胞荧光素酶表达的昼夜节律周期随年龄的增长而缩短。
Daily rhythms in physiology and behavior change with age. An unresolved question is to what extent such age-related alterations in circadian organization are driven by the central clock in the suprachiasmatic nucleus (SCN), modifying timing signals to contributing peripheral tissue oscillators, and are mediated by underlying changes in the local cellular oscillators themselves. Using a bioluminescence reporter approach, we sought to determine whether circadian clock function in human adipocytes from subcutaneous (SAT) and visceral (VAT) adipose tissues changes with age. SAT and VAT biopsies were obtained from obese individuals during gastric bypass surgeries [n = 16; body mass index: 44.8 ± 11.4 kg/m2; age: 44 ± 9 yr (range: 30–58)]. Cells were isolated and transduced with a lentiviral circadian reporter construct [brain and muscle aryl hydrocarbon receptor nuclear translocator-like:luciferase (BMAL:LUC)], and bioluminescence was recorded over a period of 3 d. Human BMAL1:LUC adipocytes displayed a robust luminescence rhythm with comparable within-individual periods in mature and preadipocytes (P > 0.05). With increasing age, the circadian period decreased in mature adipocytes (P = 0.005) (β = 4 min/yr; P < 0.05). Our ex vivo approach indicated that ageing changes the organization of endogenous circadian oscillators in human adipocytes, independent of SCN signaling.—Kolbe, I., Carrasco-Benso, M. P., López-Mínguez, J., Luján, J., Scheer, F. A. J. L., Oster, H., Garaulet, M. Circadian period of luciferase expression shortens with age in human mature adipocytes from obese patients.