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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 160-168 |
| Number of pages | 9 |
| Journal | The Journal of Clinical Endocrinology & Metabolism (JCEM) |
| Volume | 99 |
| Issue number | 1 |
| Early online date | 3 Oct 2013 |
| DOIs | |
| Publication status | Published - 2013 |
Keywords / Materials (for Non-textual outputs)
- 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1
- HUMAN ADIPOSE-TISSUE
- WEIGHT-LOSS
- IN-VIVO
- METABOLIC SYNDROME
- OBESE MEN
- FAT DIET
- HUMANS
- INSULIN
- GLUCOSE