High-fat Diet Followed by Fasting Disrupts Circadian Expression of Adiponectin Signaling Pathway in Muscle and Adipose Tissue
High-fat Diet Followed by Fasting Disrupts Circadian Expression of Adiponectin Signaling Pathway in Muscle and Adipose Tissue
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DOI：
10.1038/oby.2009.276
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发表时间：
2010-02-10
期刊：
影响因子：
6.9
通讯作者：
Froy, Oren
中科院分区：
文献类型：
--
作者：
Barnea, Maayan;Madar, Zecharia;Froy, Oren
生物钟通过调节参与代谢的蛋白质的昼夜节律表达来控制能量稳态。昼夜节律紊乱会导致肥胖和代谢紊乱。在禁食、低脂（LF）或高脂（HF）饮食下，脂肪组织、脂联素产生体和肌肉（脂联素靶组织）中脂联素信号通路的生物钟调控尚不清楚。小鼠分别饲喂低脂或高频饲料7周，最后一天禁食。检测肌肉和脂肪组织中时钟基因和脂联素代谢途径组分（mAdipoR1、mAdipoR2、mPpar α、mPpar γ、mAmpk和mAcc）的昼夜mRNA表达。利用昼夜周期内多个时间点的平均日水平，我们评估了不同脂联素信号成分的mRNA水平。此外，测定血清葡萄糖、脂联素和胰岛素。低脂饲料条件下，脂联素信号通路组分mRNA水平呈现昼夜节律性。禁食和HF饮食随后禁食破坏了这种昼夜节律表达，分别导致相提前或延迟。脂联素受体、mAmpk、mAcc、mPpar α和mPpar γ的表达水平也发生了变化，反映了脂联素信号传导的缺陷。由于过氧化物酶体增殖激活受体α (PPAR α)和mAMPK都与核心时钟机制有关，它们可以介导高频饮食下时钟基因表达的中断。反过来，生物钟影响这些脂联素信号成分的日常节律。
The circadian clock controls energy homeostasis by regulating circadian expression of proteins involved in metabolism. Disruption of circadian rhythms leads to obesity and metabolic disorders. Little is known regarding the control of the biological clock over adiponectin signaling pathway in adipose tissue, the adiponectin producer, and muscle, an adiponectin target tissue under fasting, low-fat (LF), or high-fat (HF) diet. Mice were fed LF or HF diet for 7 weeks and fasted on the last day. The circadian mRNA expression of clock genes and components of adiponectin metabolic pathway (mAdipoR1, mAdipoR2, mPpar alpha, mPpar gamma, mAmpk, and mAcc) in the muscle and adipose tissue were tested. Using average daily levels of multiple time points around the circadian cycle, we assessed mRNA levels of the different adiponectin signaling components. In addition, serum glucose, adiponectin, and insulin were measured. Under LF diet, adiponectin signaling pathway components exhibited circadian rhythmicity at the mRNA levels. Fasting and HF diet followed by fasting disrupted this circadian expression causing a phase advance or delay, respectively. Changes were also found in the expression levels of adiponectin receptor, mAmpk, mAcc, mPpar alpha, and mPpar gamma reflecting a defect in adiponectin signaling. As both peroxisome proliferator-activated receptor alpha (PPAR alpha) and mAMPK are linked to the core clock mechanism, they could mediate the disruptions seen in clock gene expression under HF diet. In turn, the circadian clock affects the daily rhythm of these adiponectin signaling components.