title: Expression of TWEAK and its receptor Fn14 in human subcutaneous adipose tissue. Relationship with other inflammatory cytokines in obesity.
abstract: TWEAK, a cytokine of the TNF family, has been found to be expressed under different inflammatory conditions but no data is available concerning the expression of this cytokine and its receptor (Fn14) in human obesity. In the present work we have evaluated the expression of many pro-inflammatory TNF system cytokines (TNF-alpha, TWEAK and their respective receptors, TNFR1, TNFR2 and Fn14) in human adipose tissue of 84 subjects some with different degree of obesity and type 2 diabetes, and its relation with inflammation by also measuring the expression of macrophage marker CD68. We detected expression of TWEAK and Fn14 in isolated mature adipocytes and in the stromovascular fraction. Additionally, we found that LPS upregulates the expression of both genes on THP-1 human monocytic cell line. TWEAK was expressed in adipose tissue of all studied subjects with no differences between obesity group, and was associated with Fn14 expression in morbid obese, mainly in women with type 2 diabetes. The data obtained here also showed that TNF-alpha and TNFR2 mRNAs were significantly more expressed in subcutaneous adipose tissue of subjects with morbid obesity compared to obese and non-obese subjects. In contrast, TNFR1 gene expression was negatively associated with BMI. Our results suggest that the expression of TNF-derived pro-inflammatory cytokines are increased in severe obesity, where macrophage infiltrate could modulate the inflammatory environment through activation of its receptors.
authors.affiliation: Endocrinology and Diabetes Unit, Research Department, University Hospital of Tarragona Joan XXIII, School of Medicine, University Rovira i Virgili, c/Mallafré Guasch 4, 43007 Tarragona, Spain.
authors.forename: M R
authors.initials: MR
authors.lastname: Chacón
authors.forename: C
authors.initials: C
authors.lastname: Richart
authors.forename: J M
authors.initials: JM
authors.lastname: Gómez
authors.forename: A
authors.initials: A
authors.lastname: Megía
authors.forename: N
authors.initials: N
authors.lastname: Vilarrasa
authors.forename: J M
authors.initials: JM
authors.lastname: Fernández-Real
authors.forename: A
authors.initials: A
authors.lastname: García-España
authors.forename: M
authors.initials: M
authors.lastname: Miranda
authors.forename: C
authors.initials: C
authors.lastname: Masdevall
authors.forename: W
authors.initials: W
authors.lastname: Ricard
authors.forename: E
authors.initials: E
authors.lastname: Caubet
authors.forename: J
authors.initials: J
authors.lastname: Soler
authors.forename: J
authors.initials: J
authors.lastname: Vendrell
mesh_terms: D000273:Adipose Tissue / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000235:genetics; D002460:Cell Line; D000074049:Cytokine TWEAK; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D000074050:TWEAK Receptor; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000074049:Cytokine TWEAK; D018836:Inflammation Mediators; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D000074050:TWEAK Receptor; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human