Open Access
BRIEF REPORT Dietary Macronutrient Content Alters Cortisol Metabolism Independently of Body Weight Changes in Obese Men
Roland Stimson,Alexandra M. Johnstone,Natalie Z.M. Homer,Deborah Wake,Nicholas M. Morton,Ruth Andrew,Gerald E. Lobley,Brian R. Walker +7 more
- 01 Jan 2007
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TL;DR: In this article, the effects of dietary macronutrients on cortisol metabolism in obese men were evaluated in two randomized, crossover studies and the results showed that a low-carbohydrate diet alters cortisol metabolism independently of weight loss.
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Abstract: CONTEXT
Dietary macronutrient composition influences cardiometabolic health independently of obesity. Both dietary fat and insulin alter glucocorticoid metabolism in rodents and, acutely, in humans. However, whether longer-term differences in dietary macronutrients affect cortisol metabolism in humans and contribute to the tissue-specific dysregulation of cortisol metabolism in obesity is unknown.
OBJECTIVE
The objective of the study was to test the effects of dietary macronutrients on cortisol metabolism in obese men.
DESIGN
The study consisted of two randomized, crossover studies.
SETTING
The study was conducted at a human nutrition unit.
PARTICIPANTS
Participants included healthy obese men. INTERVENTIONS, OUTCOME MEASURES, AND RESULTS: Seventeen obese men received 4 wk ad libitum high fat-low carbohydrate (HF-LC) (66% fat, 4% carbohydrate) vs. moderate fat-moderate carbohydrate (MF-MC) diets (35% fat, 35% carbohydrate). Six obese men participated in a similar study with isocaloric feeding. Both HF-LC and MF-MC diets induced weight loss. During 9,11,12,12-[(2)H](4)-cortisol infusion, HF-LC but not MF-MC increased 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity (rates of appearance of cortisol and 9,12,12-[(2)H](3)-cortisol) and reduced urinary excretion of 5alpha- and 5beta-reduced [(2)H](4)-cortisol metabolites and [(2)H](4)-cortisol clearance. HF-LC also reduced 24-h urinary 5alpha- and 5beta-reduced endogenous cortisol metabolites but did not alter plasma cortisol or diurnal salivary cortisol rhythm. In sc abdominal adipose tissue, 11beta-HSD1 mRNA and activity were unaffected by diet.
CONCLUSIONS
A low-carbohydrate diet alters cortisol metabolism independently of weight loss. In obese men, this enhances cortisol regeneration by 11beta-HSD1 and reduces cortisol inactivation by A-ring reductases in liver without affecting sc adipose 11beta-HSD1. Alterations in cortisol metabolism may be a consequence of macronutrient dietary content and may mediate effects of diet on metabolic health.
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Citations
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TL;DR: The data confirm that the contribution of 11&bgr;‐HSD1 to the tissue glucocorticoid pool, and the consequences of enzyme inhibition on active glucoc Corticoid concentrations, are substantial, including in the brain, and demonstrate the value of mass spectrometry imaging in pharmacokinetic and pharmacodynamic studies.
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