ABSTRACT
BACKGROUND AND AIMS: CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor involved in adipogenesis and energy homeostasis. Caloric restriction reduces CEBPA protein expression in patients with metabolic syndrome (MetS). A previous report linked rs12691 SNP in CEBPA to altered concentration of fasting triglycerides. Our objective was to assess the effects of rs12691 in glucose metabolism in Metabolic Syndrome (MetS) patients. METHODS AND RESULTS: Glucose metabolism was assessed by static (glucose, insulin, adiponectin, leptin and resistin plasma concentrations) and dynamic (disposition index, insulin sensitivity index, HOMA-IR and acute insulin response to glucose) indices, performed at baseline and after 12 weeks of 4 dietary interventions (high saturated fatty acid (SFA), high monounsaturated fatty acid (MUFA), low-fat and low-fat-high-n3 polyunsaturated fatty acid (PUFA)) in 486 subjects with MetS. Carriers of the minor A allele of rs12691 had altered disposition index (p = 0.0003), lower acute insulin response (p = 0.005) and a lower insulin sensitivity index (p = 0.025) indicating a lower insulin sensitivity and a lower insulin secretion, at baseline and at the end of the diets. Furthermore, A allele carriers displayed lower HDL concentration. CONCLUSION: The presence of the A allele of rs12691 influences glucose metabolism of MetS patients.
Subject(s)
Blood Glucose/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , Dietary Supplements , Metabolic Syndrome/genetics , Polymorphism, Single Nucleotide , Adiponectin/blood , Adult , Aged , Alleles , Blood Glucose/analysis , Body Mass Index , Body Weight , DNA/genetics , DNA/isolation & purification , Dietary Fats/administration & dosage , Fasting , Fatty Acids/administration & dosage , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids, Omega-3/administration & dosage , Female , Genotype , Humans , Insulin/blood , Insulin/metabolism , Insulin Resistance , Insulin Secretion , Leptin/blood , Lipid Metabolism/genetics , Male , Metabolic Syndrome/blood , Middle Aged , Resistin/blood , Triglycerides/bloodABSTRACT
DNA methylation is one of the important mechanisms regulating gene expression. Since beta-carotene (BC) was shown to have pro-chemotactic activity and stimulates expression of pro-angiogenic genes, this study was undertaken to define the possible changes in DNA methylation in endothelial cell and its progenitors in the presence of BC. The culture medium for human umbilical vein endothelial cells (HUVEC) and endothelial progenitor cells (EPC) was supplemented with BC (1 - 10 microM) with the presence of arachidonic acid (AA) (3 microM). Global DNA methylation tended to be lower in both endothelial cell lines, after incubation with BC and AA. HUVEC incubated with AA demonstrated the lowest DNA methylation. The decrease of DNA methylation in EPC, induced by BC, was concentration-dependent. The microarray study revealed, that the angiogenesis and homing-related genes were mostly influenced by BC and AA in investigated cells. Our results indicate that BC and AA-induced DNA hypomethylation in EPC and HUVEC, might be a mechanism which may alter gene expression in endothelial cells what in certain conditions may be connected with the suggested pro-malignant effect of this compounds.