Otukonyong Effiong E, Dube Michael G, Torto Rita, Kalra Pushpa S, Kalra Satya P
Department of Neuroscience, University of Florida, College of Medicine, PO Box 100244, Gainesville, FL 32610-0244, USA.
Obes Res. 2005 Jun;13(6):991-9. doi: 10.1038/oby.2005.116.
Sprague-Dawley rats fed a high-fat diet (HFD) are either obesity prone (OP) or obesity resistant (OR). We tested the hypothesis that differences in the ultradian rhythmic patterns of insulin and ghrelin in OP vs. OR rats promote obesity in OP rats.
Rats were fed regular chow or an HFD, and ultradian fluctuations in leptin, insulin, and ghrelin were analyzed in blood samples collected at 5-minute intervals from intrajugular cannulae of freely moving rats.
Regular chow feeding resulted in a slow weight gain accompanied by small increases in insulin and leptin and a decrease in ghrelin discharge, with only the pulse amplitude significantly altered. Similar changes were observed in OR rats, despite HFD consumption. In contrast, OP rats exhibited a high rate of weight gain and marked hyperinsulinemia, hyperleptinemia, and hypoghrelinemia; amplitude was altered, but frequency was stable. In a short-term experiment, HFD elicited similar secretory patterns of smaller magnitude even in the absence of weight gain.
We showed that three hormonal signals of disparate origin involved in energy homeostasis were secreted in discrete episodes, and only the pulse amplitude component was vulnerable to age and HFD consumption. Increases in insulin and leptin and decreases in ghrelin pulse amplitude caused by HFD were exaggerated in OP rats relative to OR rats and preceded the weight increase. These findings show that a distinct genetic predisposition in the endocrine organs of OR rats confers protection against high-fat intake-induced ultradian hypersecretion of obesity-promoting hormonal signals.
喂食高脂饮食（HFD）的斯普拉格-道利大鼠分为肥胖倾向型（OP）或肥胖抵抗型（OR）。我们检验了这样一个假设，即OP大鼠与OR大鼠相比，胰岛素和胃饥饿素的超日节律模式差异会促进OP大鼠肥胖。
给大鼠喂食常规饲料或高脂饮食，并对自由活动大鼠颈内插管每隔5分钟采集的血样中瘦素、胰岛素和胃饥饿素的超日波动进行分析。
喂食常规饲料导致体重缓慢增加，同时胰岛素和瘦素略有增加，胃饥饿素分泌减少，只有脉冲幅度有显著变化。尽管OR大鼠食用了高脂饮食，但也观察到了类似变化。相比之下，OP大鼠体重增加率高，并有明显的高胰岛素血症、高瘦素血症和低胃饥饿素血症；幅度发生了变化，但频率稳定。在一项短期实验中，即使在没有体重增加的情况下，高脂饮食也引发了幅度较小的类似分泌模式。
我们发现，参与能量稳态的三种不同来源的激素信号以离散发作的形式分泌，只有脉冲幅度成分易受年龄和高脂饮食摄入的影响。与OR大鼠相比，高脂饮食导致的OP大鼠胰岛素和瘦素增加以及胃饥饿素脉冲幅度降低更为明显，且先于体重增加。这些发现表明，OR大鼠内分泌器官中独特的遗传易感性赋予了其对高脂摄入诱导的促进肥胖激素信号超日分泌过多的保护作用。
