Stimson Roland H, Johnstone Alexandra M, Homer Natalie Z M, Wake Deborah J, Morton Nicholas M, Andrew Ruth, Lobley Gerald E, Walker Brian R
Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
J Clin Endocrinol Metab. 2007 Nov;92(11):4480-4. doi: 10.1210/jc.2007-0692. Epub 2007 Sep 4.
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.
The objective of the study was to test the effects of dietary macronutrients on cortisol metabolism in obese men.
The study consisted of two randomized, crossover studies.
The study was conducted at a human nutrition unit.
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-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-cortisol) and reduced urinary excretion of 5alpha- and 5beta-reduced (2)H-cortisol metabolites and (2)H-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.
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.
膳食常量营养素组成对心脏代谢健康的影响独立于肥胖。膳食脂肪和胰岛素均可改变啮齿动物以及人类短期内的糖皮质激素代谢。然而，膳食常量营养素的长期差异是否会影响人类的皮质醇代谢，并导致肥胖中皮质醇代谢的组织特异性失调尚不清楚。
本研究旨在测试膳食常量营养素对肥胖男性皮质醇代谢的影响。
本研究包括两项随机交叉研究。
研究在一个人类营养单位进行。
参与者包括健康肥胖男性。干预措施、结果测量和结果：17名肥胖男性接受了为期4周的随意高脂肪低碳水化合物（HF-LC）（66%脂肪，4%碳水化合物）与中等脂肪中等碳水化合物（MF-MC）饮食（35%脂肪，35%碳水化合物）。6名肥胖男性参与了一项等热量喂养的类似研究。HF-LC和MF-MC饮食均导致体重减轻。在输注9,11,12,12-(2)H-皮质醇期间，HF-LC饮食增加了11β-羟基类固醇脱氢酶1型（11β-HSD1）的活性（皮质醇和9,12,12-(2)H-皮质醇的生成速率），而MF-MC饮食则无此作用，同时HF-LC饮食还降低了5α-和5β-还原(2)H-皮质醇代谢物的尿排泄以及(2)H-皮质醇清除率。HF-LC饮食还降低了24小时尿中5α-和5β-还原内源性皮质醇代谢物，但未改变血浆皮质醇或昼夜唾液皮质醇节律。在腹部皮下脂肪组织中，11β-HSD1的mRNA和活性不受饮食影响。
低碳水化合物饮食可独立于体重减轻而改变皮质醇代谢。在肥胖男性中，这会增强11β-HSD1介导的皮质醇再生，并减少肝脏中A环还原酶介导的皮质醇失活，而不影响皮下脂肪组织中的11β-HSD1。皮质醇代谢的改变可能是膳食常量营养素含量的结果，并可能介导饮食对代谢健康的影响。
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