Maternal obesity and high leptin levels prime pro-inflammatory pathways in human cord blood leukocytes

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dc.contributor.authorKrause, Bernardo J.
dc.contributor.authorVega-Tapia, Fabian A.
dc.contributor.authorSoto-Carrasco, Gustavo
dc.contributor.authorLefever, Isidora
dc.contributor.authorLetelier, Catalina
dc.contributor.authorSaez, Claudia G.
dc.contributor.authorCastro-Rodriguez, Jose A.
dc.date.accessioned2025-01-20T17:38:25Z
dc.date.available2025-01-20T17:38:25Z
dc.date.issued2023
dc.description.abstractIntroduction: 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.funderFondecyt Regular ANID, Chile
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.placenta.2023.08.069
dc.identifier.eissn1532-3102
dc.identifier.issn0143-4004
dc.identifier.urihttps://doi.org/10.1016/j.placenta.2023.08.069
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/91706
dc.identifier.wosidWOS:001068873400001
dc.language.isoen
dc.pagina.final84
dc.pagina.inicio75
dc.revistaPlacenta
dc.rightsacceso restringido
dc.subjectMaternal obesity
dc.subjectImmune function
dc.subjectNeonatal monocytes
dc.subjectEpigenetics
dc.subjectLeptin
dc.subjectInflammation
dc.subject.ods03 Good Health and Well-being
dc.subject.ods05 Gender Equality
dc.subject.odspa03 Salud y bienestar
dc.subject.odspa05 Igualdad de género
dc.titleMaternal obesity and high leptin levels prime pro-inflammatory pathways in human cord blood leukocytes
dc.typeartículo
dc.volumen142
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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