Enhanced cortisol production rates, free cortisol, and 11β-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss
Enhanced cortisol production rates, free cortisol, and 11β-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss
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DOI：
10.1152/ajpendo.90769.2008
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发表时间：
2009-02-01
影响因子：
5.1
通讯作者：
Brunzell, John D.
中科院分区：
文献类型：
--
作者：
Purnell, Jonathan Q.;Kahn, Steven E.;Brunzell, John D.
Purnell JQ, Kahn SE, Samuels MH, Brandon D, Loriaux DL, Brunzell JD。增强的皮质醇生成率、游离皮质醇和11 β - hsd -1表达与男性内脏脂肪和胰岛素抵抗相关：减肥的影响[J] .中国生物医学工程学报，2009,31(6):557 - 557。首次发表于2008年12月2日；doi: 10.1152 / ajpendo.90769.2008。-关于内源性皮质醇的产生是否与人类内脏肥胖和胰岛素抵抗有关，存在争议。因此，我们在24名男性队列中量化了皮质醇的产生和清除率、腹部脂肪库、胰岛素敏感性和脂肪细胞基因表达。为了检验上述关系是否是肥胖的结果而不是原因，研究人员对这一较大群体中的8名男性在减肥前后进行了研究。通过稳定同位素方法和24小时采样测量每日皮质醇生成率（CPR）、游离皮质醇水平（FC）和代谢清除率（MCR）；腹腔内脂肪（IAF）和皮下脂肪（SQF）的计算机断层扫描；胰岛素敏感性（SI）频繁取样静脉葡萄糖耐量试验；和脂肪细胞11 β -羟基类固醇脱氢酶-1 （11 β - hsd -1）基因表达的定量RT-PCR皮下活检。CPR和FC增加与IAF增加相关，但与SQF和SI降低无关。11 β - hsd -1基因表达增加与IAF和SQF以及S-I降低相关。随着体重减轻，CPR、FC和MCR与基线相比没有变化；然而，在减肥过程中，体脂减少量大于瘦体重，CPR和FC与最终脂肪量成比例增加，IAF和11 β - hsd -1与基线相比下降。这些数据支持一个模型，即男性下丘脑-垂体-肾上腺活性的增加促进了选择性内脏脂肪积累和胰岛素抵抗，并可能促进饮食引起的体重减轻后的体重恢复，而SQF中11 β - hsd -1基因表达是肥胖的结果而不是原因。
Purnell JQ, Kahn SE, Samuels MH, Brandon D, Loriaux DL, Brunzell JD. Enhanced cortisol production rates, free cortisol, and 11 beta-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss. Am J Physiol Endocrinol Metab 296: E351-E357, 2009. First published December 2, 2008; doi: 10.1152/ajpendo.90769.2008.-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 (SI) by frequently sampled intravenous glucose tolerance test; and adipocyte 11 beta-hydroxysteroid dehydrogenase-1 (11 beta-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 SI. Increased 11 beta-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 11 beta-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 11 beta-HSD-1 gene expression in SQF is a consequence rather than cause of adiposity.