Elevated hypoxic inducible factor-1 alpha levels associated with metabolic disorders in children with obesity

Abstract

Abstract Objective: We aimed to examine expression and circulation levels of hypoxic inducible factor-1 (HIF1α) in children, and to evaluate its potential relationships with obesity and metabolic disorders. Methods: To begin, mRNA and protein expressions of HIF1α in 17 paired subcutaneous (SC) and omental (OM) adipose tissues from children were determined by real-time PCR and immunohistochemistry, respectively. Subsequently, anthropometric and biochemical parameters were measured in 100 normal weight children and 402 children with overweight or obesity (OV/OB). Furthermore, the serum levels of HIF1α were measured by enzyme-linked immunosorbent assay. Results: Both HIF1α mRNA and protein levels were higher in OV/OB children (p＜0.05), especially in OM adipose tissue. Additionally, serum HIF1α levels were markedly elevated in OV/OB children compared to normal children (p＜0.05). Serum HIF1α levels were positive correlated with BMI z-score, FM%, WHtR, SBP, ALT, TG, UA, and HOMA-IR. Furthermore, a binary logistic regression analysis indicated that the odds ratios the ORs for IR (OR: 1.729, 95% confidence interval [CI]: 0.571~10.056, p=0.021), NAFLD (OR: 1.176, 95% CI: 1.002~1.402 , p=0.030), and MS (OR: 2.821, 95% CI: 0.519~11.993, p=0.003) remained significant in the presence of all potential confounding variables. The receiver operating characteristic curve (ROC) of serum HIF1α levels in diagnosing children with IR, NAFLD, and MS were 0.698 (95% CI: 0.646~ 0.750, p < 0.001), 0.679 (95% CI: 0.628~0.731, p < 0.001), and 0.829 (95% CI: 0.749~0.910, p < 0.001). Conclusion: HIF1α expression in adipose tissue of children appeared to be depot specific and increased in OM of children with obesity. Elevated serum HIF1α levels may predict higher risk of obesity complications.