University/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
J Clin Endocrinol Metab. 2014 Jan;99(1):160-168. doi: 10.1210/jc.2013-2307. Epub 2013 Dec 20.
Circadian variation is a fundamental characteristic of plasma glucocorticoids, with a postprandial rise in cortisol an important feature. The diurnal rhythm is presumed to reflect alterations in hypothalamic-pituitary-adrenal axis activity; however, cortisol is produced not only by the adrenal glands but also by regeneration from cortisone by the enzyme 11β-hydroxysteroid dehydrogenase type 1, mainly in liver and adipose tissue.
We tested the contribution of peripheral cortisol regeneration to macronutrient-induced circadian variation of plasma cortisol in humans.
This was a randomized, single-blinded, crossover study.
The study was conducted at a hospital research facility.
Eight normal-weight healthy men participated in the study.
Subjects were given isocaloric energy isodense flavor-matched liquid meals composed of carbohydrate, protein, fat, or low-calorie placebo during infusion of the stable isotope tracer 9,11,12,12-[2H]4-cortisol.
Plasma cortisol increased similarly after all macronutrient meals (by ∼90 nmol/L) compared with placebo. Carbohydrate stimulated adrenal secretion and extra-adrenal regeneration of cortisol to a similar degree. Protein and fat meals stimulated adrenal cortisol secretion to a greater degree than extra-adrenal cortisol regeneration. The increase in cortisol production by 11β-hydroxysteroid dehydrogenase type 1 was in proportion to the increase in insulin. The postprandial cortisol rise was not accounted for by decreased cortisol clearance.
Food-induced circadian variation in plasma cortisol is mediated by adrenal secretion and extra-adrenal regeneration of cortisol. Given that the latter has the more potent effect on tissue cortisol concentrations and that effects on adrenal and extra-adrenal cortisol production are macronutrient specific, this novel mechanism may contribute to the physiological interplay between insulin and glucocorticoids and the contrasting effects of certain diets on postprandial metabolism.
皮质醇的昼夜节律是其基本特征之一，餐后皮质醇升高是其重要特征。该昼夜节律被认为反映了下丘脑-垂体-肾上腺轴活性的变化；然而，皮质醇不仅由肾上腺产生，还可以通过 11β-羟类固醇脱氢酶 1 型（主要在肝脏和脂肪组织中）从可的松再生。
我们检测了外周皮质醇再生对人类摄食诱导的血浆皮质醇昼夜节律变化的贡献。
这是一项随机、单盲、交叉研究。
在医院研究设施进行。
8 名正常体重的健康男性参加了这项研究。
在稳定同位素示踪剂 9,11,12,12-[2H]4-皮质醇输注期间，受试者接受等热量等能量的风味匹配的液体餐，这些液体餐由碳水化合物、蛋白质、脂肪或低热量安慰剂组成。
与安慰剂相比，所有宏量营养素餐（增加约 90 nmol/L）后，血浆皮质醇升高相似。碳水化合物刺激肾上腺分泌和皮质醇的肾上腺外再生的程度相似。蛋白质和脂肪餐刺激肾上腺皮质醇分泌的程度大于肾上腺外皮质醇再生。11β-羟类固醇脱氢酶 1 增加的皮质醇生成量与胰岛素增加量成正比。皮质醇清除率的降低不能解释餐后皮质醇升高。
食物诱导的血浆皮质醇昼夜节律变化是由肾上腺分泌和皮质醇的肾上腺外再生介导的。鉴于后者对组织皮质醇浓度的影响更大，并且对肾上腺和肾上腺外皮质醇产生的影响是特定于宏量营养素的，因此这种新机制可能有助于胰岛素和糖皮质激素之间的生理相互作用，以及某些饮食对餐后代谢的相反影响。
