1Department of Physiology, Building 13F, Monash University, Clayton, VIC 3800, Australia.
FASEB J. 2014 Jan;28(1):35-44. doi: 10.1096/fj.13-238345. Epub 2013 Sep 10.
Subjects characterized as cortisol high responders (HRs) consume more calories after stress, but it is unknown whether cortisol responsiveness predicts a propensity for obesity. Female sheep with either high or low cortisol responses to adrenocorticotropin (ACTH) were identified. Body composition was similar in HRs and cortisol low responders (LRs), but the HRs had greater (P<0.01) adiposity than did the LRs (40.5±0.7 vs. 35.8±1.4%) after high-energy feeding, despite comparable food intake. Postprandial thermogenesis in muscle temperature was 0.8 ± 0.08°C higher in the LRs than in the HRs (P<0.01), whereas feeding-induced changes in fat temperature were similar. Leptin and insulin sensitivity were similar in the HRs and LRs. Feeding lowered (P<0.001) the respiratory control ratio in muscle (HRs 9.2±0.8-5.2±1.2; LRs 8.4±0.5-5.2±0.7), indicative of increased uncoupled respiration. Also in muscle, the feeding-induced increases in uncoupling protein (UCP)-3 (fold increase: HRs, 2.4; LRs, 2.0), ryanodine 1 receptor (RyR1; fold increase: HRs 3.1; LRs 2.1), and sarcoendoplasmic reticulum Ca(2+)-dependent ATPase (fold increase: HRs 1.5; LRs 1.6) were equivalent in the HRs and LRs. Sequencing of mitochondrial DNA revealed no haplotypic differences between the 2 groups. We conclude that predisposition to obesity can be predicted by cortisol responsiveness to an ACTH challenge and that the response is due to innate differences in muscle thermogenesis.
被鉴定为皮质醇高反应者（HRs）的受试者在应激后会消耗更多卡路里，但皮质醇反应性是否能预测肥胖倾向尚不清楚。确定了对促肾上腺皮质激素（ACTH）具有高或低皮质醇反应的雌性绵羊。高能量喂养后，HRs 的体脂（40.5±0.7%）比 LRs（35.8±1.4%）更大（P<0.01），尽管摄入的食物量相当，但 HRs 的体脂含量更高，而 HRs 的体脂含量相似（P<0.01），而脂肪温度的喂养诱导变化相似。LRs 的肌肉温度餐后产热比 HRs 高 0.8 ± 0.08°C（P<0.01），而喂养诱导的脂肪温度变化相似。LRs 和 HRs 之间的瘦素和胰岛素敏感性相似。喂养降低了肌肉的呼吸控制比（HRs 9.2±0.8-5.2±1.2；LRs 8.4±0.5-5.2±0.7）（P<0.001），表明解偶联呼吸增加。同样在肌肉中，喂养诱导的解偶联蛋白（UCP）-3（倍数增加：HRs，2.4；LRs，2.0）、ryanodine 1 受体（RyR1；倍数增加：HRs，3.1；LRs，2.1）和肌浆网 Ca2+依赖性 ATP 酶（倍数增加：HRs，1.5；LRs，1.6）的增加在 HRs 和 LRs 中是等效的。线粒体 DNA 测序未发现两组之间存在单倍型差异。我们得出的结论是，肥胖的倾向可以通过对 ACTH 挑战的皮质醇反应性来预测，并且这种反应是由于肌肉产热的固有差异所致。
