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The post-prandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisol production

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalJournal of Clinical Endocrinology & Metabolism
Volume99
Issue number1
Early online date3 Oct 2013
DOIs
Publication statusPublished - 2013

Abstract

Context
Circadian variation is a fundamental characteristic of plasma glucocorticoids, with a post-prandial 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 (11β-HSD1), mainly in liver and adipose tissue.

Objective
We tested the contribution of peripheral cortisol regeneration to macronutrient-induced circadian variation of plasma cortisol in humans.

Design
Randomised single-blinded crossover study

Setting
Hospital Research Facility

Participants
Eight normal weight healthy men

Interventions
Subjects were given isocaloric energy isodense flavour-matched liquid meals composed of either carbohydrate, protein, fat or low calorie placebo during infusion of the stable isotope tracer 9,11,12,12-[2H]4-cortisol.

Outcome Measures and Results
Plasma cortisol increased similarly after all macronutrient meals (by ∼90nmol/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-HSD1 was in proportion to the increase in insulin. The post-prandial cortisol rise was not accounted for by decreased cortisol clearance.

Conclusions
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 post-prandial metabolism.

    Research areas

  • 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1, HUMAN ADIPOSE-TISSUE, WEIGHT-LOSS, IN-VIVO, METABOLIC SYNDROME, OBESE MEN, FAT DIET, HUMANS, INSULIN, GLUCOSE

ID: 10459613