title: Association of glypican-4 with body fat distribution, insulin resistance, and nonalcoholic fatty liver disease.
abstract: 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.
  
  
  METHODS
  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 < .001) and had a significant positive relationship with the waist-to-hip ratio (WHR) (r = 0.20, P = .014) and the ratio of visceral to sc fat area (r = 0.30, P < .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 = .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 = .034).
  
  
  CONCLUSIONS
  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.
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University, Seoul 152-703, Korea.
authors: H J
authors: HJ
authors: Yoo
authors: S Y
authors: SY
authors: Hwang
authors: G J
authors: GJ
authors: Cho
authors: H C
authors: HC
authors: Hong
authors: H Y
authors: HY
authors: Choi
authors: T G
authors: TG
authors: Hwang
authors: S M
authors: SM
authors: Kim
authors: Matthias
authors: M
authors: Blüher
authors: Byung-Soo
authors: BS
authors: Youn
authors: S H
authors: SH
authors: Baik
authors: K M
authors: KM
authors: Choi
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D050154:Adiposity; D000328:Adult; D000368:Aged; D050218:Body Fat Distribution; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015444:Exercise; D005234:Fatty Liver / Q000097:blood* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005260:Female; D053673:Glypicans / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D012727:Sex Characteristics; D059289:Vascular Stiffness
chemical_list: C492044:GPC4 protein, human; D053673:Glypicans