JCEM：台湾国防医学院Yi–Jen Hung等发现循环生长停滞特异性蛋白6与肥胖有关

生长停滞特异性蛋白6（Gas6）是由免疫细胞、内皮细胞、血管平滑肌细胞和脂肪细胞分泌的一种维生素K依赖蛋白。临床前研究表明Gas6和其受体TAM家族（Tyro–3,Axl,Mer）可能参与肥胖及其并发症的发病机制，包括全身炎症和胰岛素抵抗。到目前为止，Gas6/TAM系统在儿童肥胖中的临床意义所知甚少。为了确定在台湾青少年中，循环Gas6和可溶性Axl（sAxl）水平是否与肥胖、炎症和胰岛素抵抗状态有关，来自台湾国防医学院三军总医院内分泌与代谢病科的Yi–Jen Hung教授及其团队进行了一项研究，该研究发现在超重和肥胖青少年中，循环Gas6水平与肥胖、炎症和胰岛素抵抗状态紧密相关。该研究结果在线发表在2013年1月22日的美国《临床内分泌代谢杂志》（The journal of clinical endocrinology & metabolism）上。
该研究是一项横断面分析，使用的数据来自台北儿童心脏研究–Ⅲ。包括总共832例青少年（平均年龄13.3岁），分为三组：消瘦，超重和肥胖。检测循环Gas6和sAxl水平、肥胖状态、炎性标志物和胰岛素抵抗状态。
该研究结果表明，与消瘦组相比，超重和肥胖青少年循环Gas6和sAxl水平显著增加（P均＜0.05）。在超重和肥胖青少年，循环Gas6水平与体重指数Z值（P=0.045）、腰围（P＜0.001）、腰臀比（P＜0.001）、体脂含量（P=0.02）、血清超敏C反应蛋白（P=0.005）以及肿瘤坏死因子–α水平（P=0.039）呈显著正相关。在校正年龄、性别、坦纳氏期、吸烟和饮酒状态后，这种相关性仍然有意义。另外，在超重和肥胖青少年中，循环Gas6浓度每增加1ng/ml，对应胰岛素抵抗进展的风险增加15%至19%。
该研究发现，在超重和肥胖青少年中，循环Gas6水平与肥胖、炎症和胰岛素抵抗状态紧密相关。Gas6/TAM系统在儿童肥胖和肥胖相关并发症起始中的潜在作用值得进一步关注。

与肥胖相关的拓展阅读： 

• ERJ：肥胖可能降低肺炎住院患者的死亡率
• Diabetes Care：青少年肥胖者发生糖尿病风险高于成人
• Lancet Oncol：手术范围、超重或肥胖影响术后乳腺癌患者上臂淋巴水肿的发病率
• Diabetes Care：青少年期肥胖增高糖尿病风险
• NAT GENET ：肥胖基因或是黑色素瘤的风险因素 更多信息请点击：有关肥胖更多资讯

Circulating growth arrest-specific 6 protein is associated with adiposity, systemic inflammation, and insulin resistance among overweight and obese adolescents.
CONTEXT
Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein secreted by immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Preclinical studies indicate that Gas6 and its receptors of the TAM (Tyro-3, Axl, Mer) family may be involved in the pathogenesis of obesity and its complications, including systemic inflammation and insulin resistance. Until now, little has been known about the clinical significance of the Gas6/TAM system in childhood obesity.
OBJECTIVES
This study aimed to determine whether circulating Gas6 and soluble Axl (sAxl) levels are associated with adiposity, inflammation, and insulin resistance status among Taiwanese adolescents.
METHODS
Cross-sectional analyses using the data from the Taipei Children Heart Study-III were performed. A total of 832 adolescents (average age, 13.3 years) were included; they were divided into 3 groups: lean, overweight, and obese. Circulating Gas6 and sAxl levels, adiposity, inflammatory markers, and insulin resistance status were examined.
RESULTS
Levels of circulating Gas6 and sAxl were significantly higher in overweight and obese adolescents than in the lean group (both P < .05). Circulating Gas6 levels were significantly positively correlated with body mass index Z-score (P = .045), waist circumference (P < .001), waist to hip circumference ratio (P < .001), body fat mass (P = .02), serum high-sensitivity C-reactive protein (P = .005), and tumor necrosis factor-α levels (P = .039) among overweight and obese adolescents. The correlations remained significant after adjusting for age, gender, Tanner stage, smoking status, and drinking status. In addition, every 1 ng/mL increase in circulating Gas6 concentration corresponded to a 15% to 19% increase in the risk of developing insulin resistance among overweight and obese adolescents.
CONCLUSIONS
Circulating Gas6 levels are strongly associated with adiposity, inflammation, and insulin resistance status among overweight and obese adolescents. The potential role of the Gas6/TAM system in the initiation of childhood obesity and obesity-associated complications deserves further attention.