Purnell Jonathan Q, Kahn Steven E, Samuels Mary H, Brandon David, Loriaux D Lynn, Brunzell John D
Oregon Health & Science Univ., Div. of Endocrinology, Diabetes, and Clinical Nutrition, Center for the Study of Weight Regulation, L481, 3181 SW Sam Jackson Park, Portland, OR 97239, USA.
Am J Physiol Endocrinol Metab. 2009 Feb;296(2):E351-7. doi: 10.1152/ajpendo.90769.2008. Epub 2008 Dec 2.
Controversy exists as to whether endogenous cortisol production is associated with visceral obesity and insulin resistance in humans. We therefore quantified cortisol production and clearance rates, abdominal fat depots, insulin sensitivity, and adipocyte gene expression in a cohort of 24 men. To test whether the relationships found are a consequence rather than a cause of obesity, eight men from this larger group were studied before and after weight loss. Daily cortisol production rates (CPR), free cortisol levels (FC), and metabolic clearance rates (MCR) were measured by stable isotope methodology and 24-h sampling; intra-abdominal fat (IAF) and subcutaneous fat (SQF) by computed tomography; insulin sensitivity (S(I)) by frequently sampled intravenous glucose tolerance test; and adipocyte 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1) gene expression by quantitative RT-PCR from subcutaneous biopsies. Increased CPR and FC correlated with increased IAF, but not SQF, and with decreased S(I). Increased 11beta-HSD-1 gene expression correlated with both IAF and SQF and with decreased S(I). With weight loss, CPR, FC, and MCR did not change compared with baseline; however, with greater loss in body fat than lean mass during weight loss, both CPR and FC increased proportionally to final fat mass and IAF and 11beta-HSD-1 decreased compared with baseline. These data support a model in which increased hypothalamic-pituitary-adrenal activity in men promotes selective visceral fat accumulation and insulin resistance and may promote weight regain after diet-induced weight loss, whereas 11beta-HSD-1 gene expression in SQF is a consequence rather than cause of adiposity.
内源性皮质醇的产生是否与人类内脏肥胖和胰岛素抵抗相关存在争议。因此，我们对24名男性队列中的皮质醇产生和清除率、腹部脂肪堆积、胰岛素敏感性以及脂肪细胞基因表达进行了量化。为了测试所发现的关系是肥胖的结果而非原因，对该较大组中的8名男性在体重减轻前后进行了研究。通过稳定同位素方法和24小时采样测量每日皮质醇产生率（CPR）、游离皮质醇水平（FC）和代谢清除率（MCR）；通过计算机断层扫描测量腹内脂肪（IAF）和皮下脂肪（SQF）；通过频繁采样静脉葡萄糖耐量试验测量胰岛素敏感性（S(I)）；通过对皮下活检组织进行定量逆转录聚合酶链反应测量脂肪细胞11β-羟基类固醇脱氢酶-1（11β-HSD-1）基因表达。CPR和FC升高与IAF增加相关，但与SQF无关，且与S(I)降低相关。11β-HSD-1基因表达增加与IAF和SQF均相关，且与S(I)降低相关。体重减轻时，CPR、FC和MCR与基线相比未发生变化；然而，在体重减轻过程中身体脂肪的减少量大于瘦体重时，CPR和FC均与最终脂肪量成比例增加，IAF和11β-HSD-1与基线相比降低。这些数据支持这样一种模型，即男性下丘脑-垂体-肾上腺活动增加会促进选择性内脏脂肪堆积和胰岛素抵抗，并可能促进饮食诱导的体重减轻后的体重反弹，而SQF中的11β-HSD-1基因表达是肥胖的结果而非原因。
