Mistlberger R E, Marchant E G
Department of Psychology, Simon Fraser University, Burnaby BC, Canada.
Physiol Behav. 1999 Apr;66(2):329-35. doi: 10.1016/s0031-9384(98)00311-4.
This study examines the effects of the leptin receptor mutation in obese Zucker rats on entrainment of food-anticipatory rhythms to daily feeding schedules. Leptin is secreted by adipocytes in proportion to fat content, exhibits a daily rhythm in plasma that is synchronized to feeding time, and inhibits activity of arcuate neuropeptide Y neurons that stimulate feeding behavior and regulate metabolism. Activity within this neuropeptide Y system is enhanced by food deprivation and attenuated by overfeeding and diet-induced obesity. Diet-induced obesity, in turn, attenuates food-anticipatory rhythms. If the effects of obesity on food-entrained rhythms are mediated by leptin inhibition of neuropeptide Y neurons, then these rhythms may be enhanced in leptin-insensitive Zucker obese rats. Alternatively, if daily rhythms of leptin mediate the generation or entrainment of these rhythms, Zucker rats may fail to anticipate daily feedings. Zucker obese and lean rats received food for 3 h/day during the midlight period. Both groups exhibited significant food-anticipatory activity that persisted during three cycles of food deprivation, but this rhythm was significantly more robust in obese rats, when expressed as anticipation and persistence ratios, and as peak values. Anticipatory rhythms did not persist in either group when food was provided ad lib. These results indicate that central actions of leptin may mediate the inhibitory effects of obesity on the expression of food-anticipatory rhythms in rats, but do not mediate the inhibitory effects of ad lib food access, and do not serve as necessary internal entrainment cues or clock components for the food-entrainable circadian system.
本研究考察了肥胖型 Zucker 大鼠中瘦素受体突变对食物预期节律与每日进食时间表同步化的影响。瘦素由脂肪细胞按脂肪含量比例分泌，血浆中呈现出与进食时间同步的日节律，并抑制刺激进食行为和调节新陈代谢的弓状核神经肽 Y 神经元的活性。食物剥夺会增强该神经肽 Y 系统的活性，而过度喂养和饮食诱导的肥胖则会使其减弱。饮食诱导的肥胖反过来会减弱食物预期节律。如果肥胖对食物诱导节律的影响是由瘦素对神经肽 Y 神经元的抑制介导的，那么在瘦素不敏感的 Zucker 肥胖大鼠中这些节律可能会增强。或者，如果瘦素的日节律介导了这些节律的产生或同步化，Zucker 大鼠可能无法预期每日进食。Zucker 肥胖大鼠和瘦大鼠在光照中期每天进食 3 小时。两组在三个食物剥夺周期中均表现出显著的食物预期活动，且该节律持续存在，但以预期和持续率以及峰值表示时，肥胖大鼠的这种节律明显更强。当随意提供食物时，两组的预期节律均不再持续。这些结果表明，瘦素的中枢作用可能介导了肥胖对大鼠食物预期节律表达的抑制作用，但不介导随意进食的抑制作用，也不是食物可调节的昼夜节律系统必要的内部同步线索或时钟组件。
