HIF1α Elevations at Tissue and Serum Levels and Their Association With Metabolic Disorders in Children With Obesity

Abstract

Objective: We aimed to examine the expression profile and circulating level of hypoxia-inducible factor 1 alpha (HIF1α) 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 HIF1α were determined by real-time PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively.

Results: Both HIF1α mRNA and protein levels, especially in omental adipose tissue, were increased in overweight or obese (OV/OB) children (P < .05). Likewise, serum HIF1α level was remarkably higher in OV/OB children than in normal-weight children (P < .05). Serum HIF1α 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 HIF1α 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 HIF1α 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: HIF1α expression is higher in the adipose tissue, especially omental, of children with obesity than in children with normal weight. Elevated serum HIF1α level is associated with adiposity and metabolic disorder, which may predict a higher risk of obesity complications.

Keywords: adipose tissue; children; hypoxia-inducible factor 1 alpha; metabolic disorders; obesity.