RESUMEN
Obesity is a chronic inflammatory state with cytokines, adipokines, and miRNAs. The A2a-adenosine system decreases activation and cytokine release in immune cells. MiR-221 is upregulated in carcinogenesis and inflammatory processes, where its targets PTEN and ETS-1, negatively regulates the Akt pathway and induces the release of pro-inflammatory cytokines, respectively. However, the roles of the A2a-adenosine system and miR-221 in adipose tissue are unknown. The aim of this work was to evaluate the A2a-adenosine and miRNA pathways as immune modulators in adipose tissue. We collected aspirate of adipose tissue from patients with BMIâ¯<â¯25â¯kg/m2 (BMIâ¯<â¯25) and BMIâ¯≥â¯25â¯kg/m2 (BMIâ¯≥â¯25) who underwent liposuction; the adipose tissue was digested with collagenase, and then a Ficoll gradient was performed to obtain mononuclear cells from adipose tissue (MCAT). We evaluated the A2a levels by quantitative Retro-transcriptase Polymerase Chain Reaction (RT-qPCR) and flow cytometry and the A2a-adenosine function with a proliferation assay or cytokine levels in the presence or absence of NAD+, activators, and inhibitors of the system. We also analyzed miR-221, ETS-1 and PTEN levels by qRT-PCR. First, we detected that MCAT presented higher basal proliferation than mononuclear cells from peripheral blood; however, activation of the A2a receptor downregulated cell proliferation and cytokine release. Interestingly, while miR-221 was downregulated in MCAT from subjects with BMIâ¯≥â¯25 compared to BMIâ¯<â¯25, their targets ETS-1 and PTEN, were increased. In conclusion, the A2a-adenosine system is decreased in MCAT, but it maintains its function; moreover, miR-221 could participate in promoting inflammation in adipose tissue.
Asunto(s)
Tejido Adiposo/metabolismo , MicroARNs/genética , Fosfohidrolasa PTEN/genética , Receptor de Adenosina A2A/metabolismo , Adulto , Femenino , Regulación de la Expresión Génica , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , MasculinoRESUMEN
BACKGROUND: The perinatal environment has a role in the establishment of altered metabolic and inflammatory responses, and could be modulated by microRNAs regulating immune and metabolic processes. OBJECTIVE: To analyze the expression profile of four circulating microRNAs and cytokine serum concentrations in neonates born to overweight and obese women. METHODS: Pregnant women were included and grouped by pregestational body mass index (21 with normal weight, 10 overweight and 10 obese women). A peripheral blood sample was obtained from newborn infants and used to determine circulating miRNAs expression and cytokine serum concentrations. RESULTS: There were significant differences in the expression of three microRNAs between newborns of pregestational obese women and newborns from pregestational normal weight women: miR-155 (p = 0.03), miR-181a (p = 0.02) and miR-221 (p = 0.04). A significant reduction in IL-1ß (p = 0.005) expression was also found in newborns of overweight women; although this cytokine was also diminished in newborns of obese women, this was not statistically significant. An association between IL-1ß concentrations and miR-146a and miR-221 expression was also observed. CONCLUSIONS: Expression of miR-155, miR-181a and miR-221 differs in infants born to obese women compared with infants born to normal weight women. Changes in microRNA expression could participate in the epigenetic foetal programming of metabolic disorders in children born to obese women.