HIF1 Elevations at Tissue and Serum Levels and Their Association With Metabolic Disorders in Children With Obesity

Objective: We aimed to examine the expression profile and circulating level of hypoxia-inducible factor 1 alpha (HIF1 alpha) in children and the relationships with metabolic disorders.Methods: A total of 519 children were recruited, with paired subcutaneous and omental adipose tissues collected from 17 children and serum samples from the remaining children. All children underwent anthropometric and biochemical analyses. The mRNA, protein, and serum levels of HIF1 alpha were determined by real-time PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively.Results: Both HIF1 alpha mRNA and protein levels, especially in omental adipose tissue, were increased in overweight or obese (OV/OB) children (P < .05). Likewise, serum HIF1 alpha level was remarkably higher in OV/OB children than in normal-weight children (P < .05). Serum HIF1 alpha level was positively correlated with BMI z-score, fat mass percentage, waist to height ratio, systolic blood pressure, alanine aminotransferase, total triglycerides, uric acid, and homeostasis model assessment of insulin resistance (IR). Furthermore, a binary logistic regression analysis of serum HIF1 alpha level indicated that the risks for IR, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome remained significant in the presence of all potential confounding variables. Finally, the area under the receiver operating characteristic curves for serum HIF1 alpha level in children who were diagnosed with IR, NAFLD, and metabolic syndrome were 0.698 (95% CI, 0.646-0.750; P < .001), 0.679 (95% CI, 0.628-0.731; P < .001), and 0.900 (95% CI, 0.856-0.945; P < .001).Conclusion: HIF1 alpha expression is higher in the adipose tissue, especially omental, of children with obesity than in children with normal weight. Elevated serum HIF1 alpha level is associated with adiposity and metabolic disorder, which may predict a higher risk of obesity complications.