Repositorio Académico UOH

Bibliotecas Universidad de O'Higgins



Mostrar el registro sencillo del ítem

dc.contributor.author Krause, BJ
dc.contributor.author Vega-Tapia, FA
dc.contributor.author Soto-Carrasco, G
dc.contributor.author Lefever, I
dc.contributor.author Letelier, C
dc.contributor.author Saez, CG
dc.contributor.author Castro-Rodriguez, JA
dc.date.accessioned 2024-01-17T15:54:52Z
dc.date.available 2024-01-17T15:54:52Z
dc.date.issued 2023
dc.identifier.uri https://repositorio.uoh.cl/handle/611/649
dc.description.abstract Introduction: Maternal obesity alters the immune function in the offspring. We hypothesize that maternal obesity and pro-inflammatory pathways induce leptin-related genes in neonatal monocytes, whereby high leptin levels enhance their inflammatory response. Methods: Transcriptional profiles of cord blood leukocytes (CBL) in basal and pro-inflammatory conditions were studied to determine differentially expressed genes (DEG). The DNA methylation profile of CB monocytes (CBM) of neonates born to control BMI mothers and women with obesity was assayed to identify differentially methylated probes (DMP). CBM-derived macrophages were cultured with or without leptin (10-100 ng/ml) and then stimulated with lipopolysaccharide (LPS, 100 ng/ml) and interferon-gamma (20 ng/ml) to assess the induction of TNF-& alpha; and IL-10 transcripts. Results: CBL from pregnancies with obesity (CBL-Ob) showed 12,183 DEG, affecting 49 out of 78 from the leptin pathway. Control CBM exposed to LPS showed 45 leptin-related DEG, an effect prevented by the co-exposure to LPS and IL-10. Conversely, CBM-Ob showed 5279 DMP enriched in insulin- and leptin-related genes, and Lasso regression of leptin-related DMP showed high predictive value for plasma leptin levels (r2 = 0.9897) and maternal BMI categories (AUC = 1). Chronic exposure to leptin increased TNF-& alpha; and decreased IL-10 levels in control BMI samples but not in Ob-CBM. Enhanced TNF-& alpha; induction after proinflammatory stimulation was observed in leptin-treated control BMI samples. Discussion: Obesity in pregnancy is associated with a distinctive expression and DNA methylation profile of leptin-related genes in cord blood monocytes, meanwhile, leptin enhances the expression of pro-inflammatory cytokines upon stimulation with M1-skewing agents.
dc.description.sponsorship Fondecyt Regular ANID, Chile
dc.relation.uri http://dx.doi.org/10.1016/j.placenta.2023.08.069
dc.subject Maternal obesity
dc.subject Immune function
dc.subject Neonatal monocytes
dc.subject Epigenetics
dc.subject Leptin
dc.subject Inflammation
dc.title Maternal obesity and high leptin levels prime pro-inflammatory pathways in human cord blood leukocytes
dc.type Artículo
uoh.revista PLACENTA
dc.identifier.doi 10.1016/j.placenta.2023.08.069
dc.citation.volume 142
uoh.indizacion Web of Science


Ficheros en el ítem

Ficheros Tamaño Formato Ver

No hay ficheros asociados a este ítem.

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem


Colecciones


Archivos

Artículos

Tesis

Videos


Cuartiles