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 received4 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.
RCT Entities:
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 obesemen. DESIGN: The study consisted of two randomized, crossover studies. SETTING: The study was conducted at a human nutrition unit. PARTICIPANTS: Participants included healthy obesemen. INTERVENTIONS, OUTCOME MEASURES, AND RESULTS: Seventeen obesemen 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 obesemen 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 obesemen, 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.
Authors: Cara B Ebbeling; Janis F Swain; Henry A Feldman; William W Wong; David L Hachey; Erica Garcia-Lago; David S Ludwig Journal: JAMA Date: 2012-06-27 Impact factor: 56.272
Authors: A Janet Tomiyama; Traci Mann; Danielle Vinas; Jeffrey M Hunger; Jill Dejager; Shelley E Taylor Journal: Psychosom Med Date: 2010-04-05 Impact factor: 4.312
Authors: Sakamuri S S Vara Prasad; Shanmugam S Jeya Kumar; Putcha Uday Kumar; Syed S Y H Qadri; Ayyalasomayajula Vajreswari Journal: Lipids Health Dis Date: 2010-10-08 Impact factor: 3.876
Authors: Daniel M Keenan; Ferdinand Roelfsema; Bernard J Carroll; Ali Iranmanesh; Johannes D Veldhuis Journal: Am J Physiol Regul Integr Comp Physiol Date: 2009-06-17 Impact factor: 3.619
Authors: David Q Stoye; Ruth Andrew; William A Grobman; Emma K Adam; Pathik D Wadhwa; Claudia Buss; Sonja Entringer; Gregory E Miller; James P Boardman; Jonathan R Seckl; Lauren S Keenan-Devlin; Ann E B Borders; Rebecca M Reynolds Journal: J Clin Endocrinol Metab Date: 2020-03-01 Impact factor: 5.958
Authors: Roland H Stimson; Gerald E Lobley; Ioanna Maraki; Nicholas M Morton; Ruth Andrew; Brian R Walker Journal: PLoS One Date: 2010-01-19 Impact factor: 3.240