前列腺六次跨膜蛋白2在人体脂肪组织中的表达与肥胖及胰岛素抵抗相关。
Expression of six transmembrane protein of prostate 2 in human adipose tissue associates with adiposity and insulin resistance.
作者信息
Arner Peter, Stenson Britta M, Dungner Elisabeth, Näslund Erik, Hoffstedt Johan, Ryden Mikael, Dahlman Ingrid
机构信息
Karolinska Institutet, Karolinska University Hospital-Huddinge, Department of Medicine, Stockholm, Sweden.
出版信息
J Clin Endocrinol Metab. 2008 Jun;93(6):2249-54. doi: 10.1210/jc.2008-0206. Epub 2008 Apr 1.
CONTEXT
Six transmembrane protein of prostate 2 (STAMP2) is a counterregulator of adipose inflammation and insulin resistance in mice. Our hypothesis was that STAMP2 could be involved in human obesity and insulin resistance.
OBJECTIVE
The objective of the study was to elucidate the role of adipose STAMP2 expression in human obesity and insulin resistance.
DESIGN
The design was to quantify STAMP2 in human abdominal sc and omental white adipose tissue (WAT), isolated adipocytes, and stroma and in vitro differentiated preadipocytes and relate levels of STAMP2 in sc WAT to clinical and adipocyte phenotypes involved in insulin resistance.
PARTICIPANTS
Nonobese and obese women and men (n = 236) recruited from an obesity clinic or through local advertisement.
MAIN OUTCOME MEASUREMENT
Clinical measures included body mass index, body fat, total adiponectin, and homeostasis model assessment as measure of overall insulin resistance. In adipocytes we determined cell size, sensitivity of lipolysis and lipogenesis to insulin, adiponectin secretion, and inflammatory gene expression.
RESULTS
STAMP2 levels in sc and visceral WAT and adipocytes were increased in obesity (P = 0.0008-0.05) but not influenced by weight loss. Increased WAT STAMP2 levels associated with a high amount of body fat (P = 0.04), high homeostasis model assessment (P = 0.01), and large adipocytes (P = 0.02). Subjects with high STAMP2 levels displayed reduced sensitivity of adipocyte lipogenesis (P = 0.04) and lipolysis (P = 0.03) to insulin but had normal adiponectin levels. WAT STAMP2 levels correlated with expression of the macrophage marker CD68 (P = 0.0006).
CONCLUSION
Human WAT STAMP2 associates with obesity and insulin resistance independently of adiponectin, but the role of STAMP2 in obesity and its complications seems different from that in mice.
背景
前列腺六跨膜蛋白2(STAMP2)是小鼠脂肪炎症和胰岛素抵抗的一种反向调节因子。我们的假设是STAMP2可能与人类肥胖和胰岛素抵抗有关。
目的
本研究的目的是阐明脂肪组织中STAMP2表达在人类肥胖和胰岛素抵抗中的作用。
设计
对人类腹部皮下和网膜白色脂肪组织(WAT)、分离的脂肪细胞、基质以及体外分化的前脂肪细胞中的STAMP2进行定量,并将皮下WAT中STAMP2的水平与参与胰岛素抵抗的临床和脂肪细胞表型相关联。
参与者
从肥胖诊所或通过当地广告招募的非肥胖和肥胖女性及男性(n = 236)。
主要观察指标
临床指标包括体重指数、体脂、总脂联素以及作为整体胰岛素抵抗指标的稳态模型评估。在脂肪细胞中,我们测定了细胞大小、脂解和脂肪生成对胰岛素的敏感性、脂联素分泌以及炎症基因表达。
结果
肥胖时皮下和内脏WAT及脂肪细胞中的STAMP2水平升高(P = 0.0008 - 0.05),但不受体重减轻的影响。WAT中STAMP2水平升高与大量体脂(P = 0.04)、高稳态模型评估(P = 0.01)和大脂肪细胞(P = 0.02)相关。STAMP2水平高的受试者脂肪细胞脂肪生成(P = 0.04)和脂解(P = 0.03)对胰岛素的敏感性降低,但脂联素水平正常。WAT中STAMP2水平与巨噬细胞标志物CD68的表达相关(P = 0.0006)。
结论
人类WAT中的STAMP2与肥胖和胰岛素抵抗相关,且独立于脂联素,但STAMP2在肥胖及其并发症中的作用似乎与小鼠不同。