Abnormalities of the hypothalamic-pituitary-adrenal axis in nondepressed women with abdominal obesity and relations with insulin resistance: Evidence for a central and a peripheral alteration
Abnormalities of the hypothalamic-pituitary-adrenal axis in nondepressed women with abdominal obesity and relations with insulin resistance: Evidence for a central and a peripheral alteration
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DOI：
10.1210/jc.85.11.4093
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发表时间：
2000-11-01
影响因子：
5.8
通讯作者：
Pasquali, R
中科院分区：
文献类型：
--
作者：
Vicennati, V;Pasquali, R
我们以前已经表明，腹部体脂分布（A-BFD）的妇女有一个过度活跃的下丘脑-垂体-肾上腺（HPA）轴。然而，我们没有考虑焦虑和/或抑郁的存在，肥胖受试者的常见表现。焦虑和抑郁可能与皮质醇分泌过多有关，并可能是评估不同肥胖表型HPA轴的混杂因素。在这项研究中，非抑郁症肥胖妇女腹部和外周（P-BFD）的体脂分布和控制瘦组进行了CRH/AVP刺激试验促肾上腺皮质激素和皮质醇的测定。此外，所有妇女都进行了代谢评估，并测定了尿游离皮质醇（UFC）排泄量。刺激后，ACTH和皮质醇的反应在A-BFD比在P-BFD和对照组。在所有肥胖患者中，ACTH曲线下面积（r（2）= 0.366; P = 0.003）或皮质醇曲线下面积（r（2）= 0.378; P = 0.043）与稳态胰岛素抵抗指数呈正相关。出乎意料的是，A-BFD的UFC/m2值显著低于P-BFD（P < 0.05）。A-BFD组UFC排泄降低与皮质醇清除率增加一致，这反过来可能导致HPA轴过度活跃，作为一种适当的代偿机制。另一方面，其他机制，可能是中央的起源，如过度驱动的CRH-ACTH系统的慢性环境应激因素，可能涉及在确定HPA过度反应腹型肥胖。总之，这项研究表明，腹部肥胖表型的妇女的特点是中央和周边的HPA轴活动的改变。
We have previously shown that women with abdominal body fat distribution (A-BFD) have a hyperactive hypothalamic-pituitary-adrenal (HPA) axis. However, we did not consider the presence of anxiety and/or depression, common manifestations in obese subjects. Anxiety and depression may be associated with oversecretion of cortisol and could represent a confounding factor in the evaluation of the HPA axis in different obesity phenotypes. In this study nondepressed obese women with abdominal and peripheral (P-BFD) body fat distribution and a control lean group underwent a CRH/AVP stimulation test for ACTH and cortisol determinations. Moreover, all women underwent metabolic evaluation and had their urinary free cortisol (UFC) excretion measured. After the stimuli, ACTH and cortisol responded more in the A-BFD than in the P-BFD and control groups. A positive correlation was found between either ACTH area under the curve (r(2) = 0.366; P = 0.003) or cortisol area under the curve (r(2) = 0.378; P = 0.043) and the homeostasis insulin resistance index in all obese patients. Unexpectedly, A-BFD had significantly lower UFC per m(2) values than P-BFD (P < 0.05). Lowered UFC excretion in the A-BFD group is in keeping with an increased cortisol clearance, which, in turn, may lead to HPA axis hyperactivity as an appropriate compensatory mechanism. On the other hand, other mechanisms, possibly central in origin, such as overdriving of the CRH-ACTH system to chronic environmental stress factors, may be involved in determining HPA overresponsiveness in abdominal obesity. In conclusion, this study suggests that women with the abdominal obesity phenotype are characterized by both central and peripheral alterations of the HPA axis activity.