ABSTRACT
BACKGROUND: Nuclear receptor coactivator 2 (NCOA2) gene plays an important role in adipogenesis and lipid metabolism. NCOA2 gene null mice exhibited less fat accumulation and lower serum lipid levels, and were protected against obesity. Few studies are known to have analyzed the association of NCOA2 gene single nucleotide polymorphisms with obesity and serum lipid profile. Our study aimed to evaluate the association of NCOA2 gene polymorphisms with the risk of obesity and dyslipidemia in the Chinese Han population. METHODS: Two NCOA2 gene polymorphisms (rs41391448 and rs10504473) were selected and genotyped in a Chinese Han cohort with 529 participants. The effect of different genotypes on BMI and serum lipid levels (TG, TC, LDL-C and HDL-C) was performed by the analysis of covariance. Association of NCOA2 polymorphisms with obesity and dyslipidemia was assessed by odds ratios (OR) and 95% confidence intervals (CI) under the unconditional logistic regression analysis. RESULTS: Significant association was observed between rs10504473 polymorphism and obesity under the recessive model (OR = 1.88, 95% CI 1.02-3.45, P = 0.047; adjusted OR = 1.87, 95% CI 1.02-3.44, P = 0.048). However, no association remained significant after Bonferroni correction. CONCLUSION: Our study suggests a possible association between NCOA2 rs10504473 polymorphism and obesity, and this SNP may influence the susceptibility of obesity in the Chinese Han population.
Subject(s)
Asian People/genetics , Dyslipidemias/genetics , Nuclear Receptor Coactivator 2/genetics , Obesity/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Body Mass Index , Chi-Square Distribution , China/epidemiology , Dyslipidemias/blood , Dyslipidemias/diagnosis , Dyslipidemias/ethnology , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Lipids/blood , Logistic Models , Male , Middle Aged , Obesity/blood , Obesity/diagnosis , Obesity/ethnology , Odds Ratio , Phenotype , Risk FactorsABSTRACT
OBJECTIVE: Vascular cells, particularly endothelial cells, adopt aerobic glycolysis to generate energy to support cellular functions. The effect of endothelial glycolysis on angiogenesis remains unclear. 6-Phosphofructo-2-kinase/fructose-2, 6-bisphosphatase, isoform 3 (PFKFB3) is a critical enzyme for endothelial glycolysis. By blocking or deleting PFKFB3 in endothelial cells, we investigated the influence of endothelial glycolysis on angiogenesis both in vitro and in vivo. APPROACH AND RESULTS: Under hypoxic conditions or after treatment with angiogenic factors, endothelial PFKFB3 was upregulated both in vitro and in vivo. The knockdown or overexpression of PFKFB3 suppressed or accelerated endothelial proliferation and migration in vitro, respectively. Neonatal mice from a model of oxygen-induced retinopathy showed suppressed neovascular growth in the retina when endothelial PFKFB3 was genetically deleted or when the mice were treated with a PFKFB3 inhibitor. In addition, tumors implanted in mice deficient in endothelial PFKFB3 grew more slowly and were provided with less blood flow. A lower level of phosphorylated protein kinase B was observed in PFKFB3-knockdown endothelial cells, which was accompanied by a decrease in intracellular lactate. The addition of lactate to PFKFB3-knockdown cells rescued the suppression of endothelial proliferation and migration. CONCLUSIONS: The blockade or deletion of endothelial PFKFB3 decreases angiogenesis both in vitro and in vivo. Thus, PFKFB3 is a promising target for the reduction of endothelial glycolysis and its related pathological angiogenesis.
