nature-medicine201212-2

美国宾西法尼亚大学的研究人员检测了小鼠脂肪细胞中的一个生物钟基因Arntl。当习惯于夜间饮食的小鼠的进食时间改变时,该基因会导致小鼠肥胖,这一发现阐明了人类肥胖的复杂成因。

-2012年12月《自然-医学》


中文翻译


【题目】特异性敲除肥胖小鼠脂肪细胞的生物钟基因Arntl

【译文】脂肪细胞以甘油三酯的形式储存多余能量,并将所存储能量水平信息发送至脑部。本研究表明特异性敲除脂肪细胞中的Arntl基因(又名Bmal1,一种编码核心分子生物钟组分的基因),结果会会导致小鼠肥胖,伴随食物摄取昼夜节律颠倒,但当在肝细胞和胰岛中敲除Arntl基因时,我们并未观察到如此的结果。调控食欲的下丘脑神经肽的表达变化与从脂肪细胞到中枢神经系统以定时摄氏行为的反馈相一致。脂肪细胞生物钟基因的消除与脂肪细胞甘油三酯中多不饱和脂肪酸的数量减少相关。突变体和野生小鼠之间的这种差异反映在调控摄食的下丘脑神经元中多不饱和脂肪酸和未酯化脂肪酸的循环浓度上。因此,本研究揭示了脂肪细胞生物钟基因在能量调控的短暂组织中的作用,阐明了定时蛋白作为脂肪细胞下丘脑作用轴的一种调控因子的作用,并表明了定时摄食对体重的影响。

英文原稿


[Title]: Obesity in mice with adipocyte-specific deletion of clock component Arntl

[Authors]:Georgios K Paschos,1 Salam Ibrahim,1 Wen-Liang Song,1 Takeshige Kunieda,1 Gregory Grant,1 Teresa M Reyes,1 Christopher A Bradfield,2 Cheryl H Vaughan,3 Michael Eiden,4 Mojgan Masoodi,4 Julian L Griffin,4 Fenfen Wang,5 John A Lawson1 & Garret A FitzGerald1

[Abstract]Adipocytes store excess energy in the form of triglycerides and signal the levels of stored energy to the brain. Here we show that adipocyte-specific deletion of Arntl (also known as Bmal1), a gene encoding a core molecular clock component, results in obesity in mice with a shift in the diurnal rhythm of food intake, a result that is not seen when the gene is disrupted in hepatocytes or pancreatic islets. Changes in the expression of hypothalamic neuropeptides that regulate appetite are consistent with feedback from the adipocyte to the central nervous system to time feeding behavior. Ablation of the adipocyte clock is associated with a reduced number of polyunsaturated fatty acids in adipocyte triglycerides. This difference between mutant and wild-type mice is reflected in the circulating concentrations of polyunsaturated fatty acids and nonesterified polyunsaturated fatty acids in hypothalamic neurons that regulate food intake. Thus, this study reveals a role for the adipocyte clock in the temporal organization of energy regulation, highlights timing as a modulator of the adipocyte-hypothalamic axis and shows the impact of timing of food intake on body weight.

原文地址

http://www.nature.com/nm/journal/v18/n12/abs/nm.2979.html

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