High-fat feeding alters the clock synchronization to light
High-fat feeding alters the clock synchronization to light
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DOI：
10.1113/jphysiol.2008.159566
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发表时间：
2008-12-15
影响因子：
5.5
通讯作者：
Challet, Etienne
中科院分区：
文献类型：
--
作者：
Mendoza, Jorge;Pevet, Paul;Challet, Etienne
高脂肪喂养啮齿动物导致代谢异常，模仿人类代谢综合征，包括肥胖和胰岛素抵抗。这些代谢性疾病与许多生理功能的时间组织改变有关。位于视交叉上核的主生物钟控制大多数生理功能和代谢过程。此外，在某些进食条件下（低热量饮食），代谢线索能够改变视交叉上钟对光的反应。为了确定高脂肪喂养（高热量饮食）是否也会影响视交叉上时钟的重置特性，我们研究了高脂肪或食物（低脂）饮食喂养3个月的小鼠的光同步，使用车轮运行活动和体温节律作为每日相位标记（即视交叉上时钟的指针）。与对照饮食相比，用高脂肪饮食喂养的小鼠表现出增加的体重指数、高瘦素血症、更高的血糖和增加的胰岛素血症。同时，高脂肪喂养导致受损的调整，当地时间的光重置。在行为和生理水平上，这些改变包括“时差”测试（6小时先进的光-暗周期）后行为和体温节律的重新夹带速率较慢，以及对光的相位推进反应减少。在分子水平上，光诱导的相位偏移已经与视交叉上细胞内的c-FOS（即早期基因c-fos的蛋白产物）的高诱导和细胞外信号调节激酶I/II（P-ERK）的磷酸化相关。在喂食高脂饮食的小鼠中，视交叉上核中c-FOS和P-ERK的光诱导显著降低。综上所述，目前的数据表明，高脂肪喂养修改昼夜同步光。
High-fat feeding in rodents leads to metabolic abnormalities mimicking the human metabolic syndrome, including obesity and insulin resistance. These metabolic diseases are associated with altered temporal organization of many physiological functions. The master circadian clock located in the suprachiasmatic nuclei controls most physiological functions and metabolic processes. Furthermore, under certain conditions of feeding (hypocaloric diet), metabolic cues are capable of altering the suprachiasmatic clock's responses to light. To determine whether high-fat feeding (hypercaloric diet) can also affect resetting properties of the suprachiasmatic clock, we investigated photic synchronization in mice fed a high-fat or chow (low-fat) diet for 3 months, using wheel-running activity and body temperature rhythms as daily phase markers (i.e. suprachiasmatic clock's hands). Compared with the control diet, mice fed with the high-fat diet exhibited increased body mass index, hyperleptinaemia, higher blood glucose, and increased insulinaemia. Concomitantly, high-fat feeding led to impaired adjustment to local time by photic resetting. At the behavioural and physiological levels, these alterations include slower rate of re-entrainment of behavioural and body temperature rhythms after 'jet-lag' test (6 h advanced light-dark cycle) and reduced phase-advancing responses to light. At a molecular level, light-induced phase shifts have been correlated, within suprachiasmatic cells, with a high induction of c-FOS, the protein product of immediate early gene c-fos, and phosphorylation of the extracellular signal-regulated kinases I/II (P-ERK). In mice fed a high-fat diet, photic induction of both c-FOS and P-ERK in the suprachiasmatic nuclei was markedly reduced. Taken together, the present data demonstrate that high-fat feeding modifies circadian synchronization to light.