Sex-Specific Regulation of Inflammation and Metabolic Syndrome in Obesity

Rob ter Horst, Inge C. L. van den Munckhof, Kiki Schraa, Raul Aguirre-Gamboa, Martin Jaeger, Sanne P. Smeekens, Tessa Brand, Heidi Lemmers, Helga Dijkstra, Tessel E. Galesloot, Jacqueline de Graaf, Ramnik J. Xavier, Yang Li, Leo A. B. Joosten, Joost H. W. Rutten, Mihai G. Netea, Niels P. Riksen*

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    70 Citaten (Scopus)
    76 Downloads (Pure)


    Objective: Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity. Approach and Results: Three hundred two individuals were included, half with a BMI 27 to 30 kg/m(2)and half with a BMI>30 kg/m(2), 45% were women. The presence of metabolic syndrome was assessed according to the National Cholesterol Education Program-ATPIII criteria, and inflammation was studied using circulating markers of inflammation, cell counts, and ex vivo cytokine production capacity of isolated immune cells. Additionally, lipidomic and metabolomic data were gathered, and subcutaneous fat biopsies were histologically assessed. Metabolic syndrome is associated with an increased inflammatory profile that profoundly differs between women and men: women with metabolic syndrome show a lower concentration of the anti-inflammatory adiponectin, whereas men show increased levels of several pro-inflammatory markers such as IL (interleukin)-6 and leptin. Adipose tissue inflammation showed similar sex-specific associations with these markers. Peripheral blood mononuclear cells isolated from men, but not women, with metabolic syndrome display enhanced cytokine production capacity. Conclusions: We identified sex-specific pathways that influence inflammation in obesity. Excessive production of proinflammatory cytokines was observed in men with metabolic syndrome. In contrast, women typically showed reduced levels of the anti-inflammatory adipokine adiponectin. These different mechanisms of inflammatory dysregulation between women and men with obesity argue for sex-specific therapeutic strategies.

    Originele taal-2English
    Pagina's (van-tot)1787-1800
    Aantal pagina's14
    TijdschriftArteriosclerosis thrombosis and vascular biology
    Nummer van het tijdschrift7
    StatusPublished - jul.-2020

    Citeer dit