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Submitted on March 27, 2007
Accepted on August 23, 2007
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, Scotland, UK; Division of Obesity and Metabolic Health, Rowett Research Institute, Aberdeen, Scotland, UK; Mass Spectrometry Core Laboratory, Wellcome Trust Clinical Research Facility, Queen's Medical Research Institute, Edinburgh, Scotland, UK
* To whom correspondence should be addressed. E-mail: Roland.Stimson{at}ed.ac.uk.
Context Dietary macronutrient composition influences cardio-metabolic 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 To test effects of dietary macronutrients on cortisol metabolism in obese men.
Design Two randomized crossover studies.
Setting A Human Nutrition Unit.
Participants Healthy obese men.
Interventions, Outcome Measures and Results 17 obese men received 4 weeks ad libitum high fat-low carbohydrate (HF-LC) (66% fat, 4% carbohydrate) versus moderate fat-moderate carbohydrate (MF-MC) diets (35% fat, 35% carbohydrate). 6 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-[2H]4-cortisol infusion, HF-LC but not MF-MC increased 11
-HSD1 activity (rates of appearance of cortisol and 9,12,12-[2H]3-cortisol) and reduced urinary excretion of 5
- and 5-reduced [2H]4-cortisol metabolites and [2H]4-cortisol clearance. HF-LC also reduced 24 h urinary 5- and 5-reduced endogenous cortisol metabolites, but did not alter plasma cortisol or diurnal salivary cortisol rhythm. In subcutaneous abdominal adipose tissue, 11-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 11-HSD1 and reduces cortisol inactivation by A-ring reductases in liver without affecting subcutaneous adipose 11-HSD1. Alterations in cortisol metabolism may be a consequence of macronutrient dietary content and may mediate effects of diet on metabolic health.
-hydroxysteroid dehydrogenase •
Diet •
Insulin •
Weight Loss
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