title: Circulating growth arrest-specific 6 protein is associated with adiposity, systemic inflammation, and insulin resistance among overweight and obese adolescents.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 114, Taiwan, Republic of China.
authors: Fone-Ching
authors: FC
authors: Hsiao
authors: Yuh-Feng
authors: YF
authors: Lin
authors: Po-Shiuan
authors: PS
authors: Hsieh
authors: Nain-Feng
authors: NF
authors: Chu
authors: Yi-Shing
authors: YS
authors: Shieh
authors: Chang-Hsun
authors: CH
authors: Hsieh
authors: Chien-Hsing
authors: CH
authors: Lee
authors: Yi-Jen
authors: YJ
authors: Hung
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D009765:Obesity / Q000097:blood; D050177:Overweight / Q000097:blood*; D055105:Waist Circumference; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D001786:Blood Glucose; D002097:C-Reactive Protein; D036341:Intercellular Signaling Peptides and Proteins; D000099255:Growth Arrest-Specific Protein 6