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 nonalcoholic fatty liver disease (NAFLD) in nondiabetic Asian subjects.
Design and Participants:We analyzed baseline cross-sectional data from the Korean Sarcopenic Obesity Study, 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 Ͻ .001) and had a significant positive relationship with the waist-to-hip ratio (WHR) (r ϭ 0.20, P ϭ .014) and the ratio of visceral to sc fat area (r ϭ 0.30, P Ͻ .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 ϭ .017, R 2 ϭ 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 ϭ .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. A dipose tissue plays an important role in controlling systemic energy homeostasis through the secretion of various adipokines that interact with the brain, pancreas, skeletal muscle, and liver (1). Because visceral adipose tissue is more pathogenic than sc adipose tissue, the site of fat accumulation plays a pivotal role in metabolic disorders (2). However, little is known about the factors that determine sites of fat accumulation. Recently, Gesta et al found that glypican-4 is differentially expressed in visceral and sc adipose tissue, and that its expression in Abbreviations: AST, aspartate aminotransferase; baPWV, brachial ankle pulse wave velocity; BMI, body mass index; HOMA-IR, homeostasis model assessment of insulin resistance; NAFLD, nonalcoholic fatty liver disease; VFA/SFA, ratio of visceral to sc fat area; WHR, waist-to-hip ratio.