JCEM：NAFLD女性的循环蛋白聚糖–4水平增加

蛋白聚糖–4被认为是一种新型的能够增强胰岛素信号通路和调节脂肪细胞分析的脂肪因子。为了探讨在非糖尿病的亚洲人，蛋白聚糖–4与身体组成、胰岛素抵抗、动脉硬化和非酒精性脂肪性肝病（NAFLD）的关系，来自韩国高丽大学古鲁医院内分泌代谢科的Kyung Mook Choi教授及其团队进行了一项研究，该研究发现在NAFLD女性，循环蛋白聚糖–4水平增加，并与体脂分布、胰岛素抵抗和动脉硬化有关。该研究结果在线发表在2013年4月30日的美国《临床内分泌代谢杂志》上。
该研究中，对韩国肌萎性肥胖研究（一项进行中的前瞻性队列研究）的基线横断面数据进行分析。通过非增强CT使用肝衰减指数诊断NAFLD。同时检测3个月有氧和抗阻联合锻炼计划对蛋白聚糖–4水平和心血管代谢危险因素的影响。
该研究结果表明，男性的循环蛋白聚糖–4水平高于女性（1.83[1.19,2.78] ng/ml vs 1.17[0.66,2.00]ng/ml,P＜0.001）,并与腰臀比（WHR）（r=0.20,P=0.014)和内脏与皮下脂肪面积比值（r=0.30,P<0.001)呈显著正相关。此外，通过多元logistic回归分析，女性蛋白聚糖–4水平与心血管代谢危险因素包括胰岛素抵抗和动脉硬化有关，并与NAFLD独立相关（P=0.017，R2=0.33）。3个月联合锻炼计划显著改善多个心血管代谢参数，并降低视黄醇结合蛋白–4水平。锻炼计划后，蛋白聚糖–4水平的变化在WHR增加的受试者与WHR降低的受试者之间有显著性差异（P=0.034）。
该研究发现，循环蛋白聚糖4水平有明显的性别差异。循环蛋白聚糖4水平在NAFLD女性中增加，并与体脂分布、胰岛素抵抗和动脉硬化有关。

Association of Glypican-4 with Body Fat Distribution, Insulin Resistance, and Non-Alcoholic Fatty Liver Disease.
Abstract
Context and Objective:Glypican-4 was identified as a novel adipokine capable of enhancing insulin signaling and modulating adipocyte differentiation. We investigated associations between glypican-4 and body composition, insulin resistance, arterial stiffness, and non-alcoholic fatty liver disease (NAFLD) in non-diabetic Asian subjects.Design and Participants:We analyzed baseline cross-sectional data from the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective cohort study. NAFLD was diagnosed by unenhanced computed tomography using the liver attenuation index. We also examined the effects of a 3-month combined aerobic and resistance exercise program on glypican-4 levels and cardiometabolic risk factors.Results:Circulating glypican-4 levels were higher in men than in women (1.83 [1.19, 2.78] ng/ml vs. 1.17 [0.66, 2.00] ng/ml, P <0.001) and had a significant positive relationship with the waist-to-hip ratio (WHR) (r = 0.20, P = 0.014) and the ratio of visceral to subcutaneous fat area (VFA/SFA) (r = 0.30, P <0.001). Furthermore, glypican-4 levels in women were correlated with cardiometabolic risk factors including insulin resistance and arterial stiffness, and were independently associated with NAFLD by multiple logistic regression analysis (P = 0.017, R2 = 0.33). The 3-month combined exercise training program significantly improved several cardiometabolic parameters and reduced retinol binding protein-4 levels. Changes in glypican-4 levels after the exercise program were significantly different between subjects with an increased WHR compared with those with a decreased WHR (P = 0.034).Conclusion:A gender-based difference in circulating glypican-4 levels was apparent as these were increased in women with NAFLD and related to body fat distribution, insulin resistance, and arterial stiffness.