Changes in adenosine 5'-monophosphate-activated protein kinase as a mechanism of visceral obesity in Cushing's syndrome.
Changes in adenosine 5'-monophosphate-activated protein kinase as a mechanism of visceral obesity in Cushing's syndrome.
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DOI：
10.1210/jc.2008-1297
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Korbonits M
中科院分区：
文献类型：
--
作者：
Kola B;Christ-Crain M;Lolli F;Arnaldi G;Giacchetti G;Boscaro M;Grossman AB;Korbonits M
代谢综合征的特征如向心性肥胖伴胰岛素抵抗和血脂异常是库欣综合征的典型体征和长期糖皮质激素治疗的常见副作用。腺苷酸活化蛋白激酶（AMPK），一种脂质和碳水化合物代谢以及食欲的关键调节酶，参与过量糖皮质激素的有害代谢作用的发展，但没有人类的数据。在目前的研究中，我们证明了高糖皮质激素水平对库欣综合征患者脂肪组织样本AMPK活性的影响。在11例库欣综合征患者、9例性别、年龄和体重匹配的肾上腺偶发瘤患者和4例非内分泌相关腹部手术患者的腹部手术切除的内脏脂肪组织中评估AMPK活性和脂质代谢相关基因的mRNA表达。库欣综合征患者内脏脂肪组织中AMPK活性比偶发瘤和对照组低70%（分别为P = 0.007和P<0.001）。库欣综合征患者AMPK脂肪酸合酶和磷酸烯醇丙酮酸羧激酶下游靶点上调。AMPK活性与0900 h血清皮质醇和尿游离皮质醇呈负相关。我们的数据表明，糖皮质激素抑制脂肪组织中的AMPK活性，这表明了一种新的机制来解释内脏脂肪组织的沉积以及在医源性或内源性库欣综合征患者中观察到的随之而来的中心性肥胖。
Features of the metabolic syndrome such as central obesity with insulin resistance and dyslipidemia are typical signs of Cushing’s syndrome and common side effects of prolonged glucocorticoid treatment. AMP-activated protein kinase (AMPK), a key regulatory enzyme of lipid and carbohydrate metabolism as well as appetite, is involved in the development of the deleterious metabolic effects of excess glucocorticoids, but no data are available in humans. In the current study, we demonstrate the effect of high glucocorticoid levels on AMPK activity of human adipose tissue samples from patients with Cushing’s syndrome. AMPK activity and mRNA expression of genes involved in lipid metabolism were assessed in visceral adipose tissue removed at abdominal surgery of 11 patients with Cushing’s syndrome, nine sex-, age-, and weight-matched patients with adrenal incidentalomas, and in visceral adipose tissue from four patients with non-endocrine-related abdominal surgery. The patients with Cushing’s syndrome exhibited a 70% lower AMPK activity in visceral adipose tissue as compared with both incidentalomas and control patients (P = 0.007 and P<0.001, respectively). Downstream targets of AMPK fatty acid synthase and phosphoenol-pyruvate carboxykinase were up-regulated in patients with Cushing’s syndrome. AMPK activity was inversely correlated with 0900 h serum cortisol and with urinary free cortisol. Our data suggest that glucocorticoids inhibit AMPK activity in adipose tissue, suggesting a novel mechanism to explain the deposition of visceral adipose tissue and the consequent central obesity observed in patients with iatrogenic or endogenous Cushing’s syndrome.
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影响因子：
--
作者：
Hawley SA;Boudeau J;Reid JL;Mustard KJ;Udd L;Mäkelä TP;Alessi DR;Hardie DG
通讯作者：
Hardie DG
影响因子：
56.9
作者：
Shaw, RJ;Lamia, KA;Cantley, LC
通讯作者：
Cantley, LC
影响因子：
27.4
作者：
Gudbjornsson, B;Juliusson, UI;Gudjonsson, FV
通讯作者：
Gudjonsson, FV
影响因子：
5.8
作者：
Arnaldi, G;Angeli, A;Boscaro, M
通讯作者：
Boscaro, M
影响因子：
5.8
作者：
Mantero, F;Terzolo, M;Angeli, A
通讯作者：
Angeli, A