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

内科学 胰岛素抵抗 代谢综合征 内分泌学 医学 脂肪组织 尿酸 脂肪肝 腰围 肥胖 超重 疾病
作者
Nan Zhou,Zheng Wen,Peng Lü,Shujun Gao,Yunfei Shi,Mengyao Cao,Yan Xu,Bin Sun,Xiaonan Li
出处
期刊:The Journal of Clinical Endocrinology and Metabolism [The Endocrine Society]
卷期号:109 (5): 1241-1249
标识
DOI:10.1210/clinem/dgad710
摘要

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.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.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).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.
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