%0 Journal Article
%A Maymó-Masip, Elsa
%A Fernández-Veledo, Sonia
%A García España, Antonio
%A Vázquez-Carballo, Ana
%A Tinahones, Francisco José
%A García-Fuentes, Eduardo
%A Garrifo-Sánchez, Lourdes
%A Rodríguez, María del Mar
%A Vendrell, Joan
%A Chacón, Matilde R
%T The rise of soluble TWEAK levels in severely obese subjects after bariatric surgery may affect adipocyte-cytokine production induced by TNFα.
%D 2013
%@ 0021-972X
%U http://hdl.handle.net/10668/1695
%X CONTEXTSoluble TNF-like weak inducer of apoptosis (sTWEAK) is generated by the intracellular proteolytic cleavage of full-length membrane-bound TNF-like weak inducer of apoptosis (mTWEAK). sTWEAK levels are reduced in diseases with an inflammatory component. Additionally, sTWEAK hampers TNFα activity in human cells.OBJECTIVESThe objectives of the study were as follows: 1) to determine circulating sTWEAK in severe obesity and after bariatric surgery; 2) to study m/sTWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14) protein expression in sc adipose tissue (SAT) of severely obese subjects, in SAT stromal vascular fraction (SVF), and isolated adipocytes and in human monocyte-derived macrophages; and 3) to explore, on human adipocytes, the sTWEAK effect on TNFα proinflammatory activity.DESIGNsTWEAK levels were measured in cohort 1: severely obese subjects (n = 23) and a control group (n = 35); and in cohort 2: (n = 23) severely obese subjects before and after surgery. The m/sTWEAK and Fn14 expressions were determined in SAT biopsies, SVF, and isolated adipocytes from severely obese and control subjects and in human monocyte-derived macrophages. In human primary cultured adipocytes, sTWEAK pretreated and TNFα challenged, IL-6, IL-8, and adiponectin protein and gene expressions were determined and nuclear factor-κ B and MAPK signaling analyzed.RESULTSsTWEAK levels were reduced in severely obese subjects. After surgery, sTWEAK levels rose in 69% of patients. mTWEAK protein expression was increased in SAT and SVF of severely obese subjects, whereas Fn14 was up-regulated in isolated adipocytes. M2 human monocyte-derived macrophages overexpress mTWEAK. In human adipocytes, sTWEAK down-regulates TNFα cytokine production by hampering TNFα intracellular signaling events.CONCLUSIONThe decrease of sTWEAK in severely obese patients may favor the proinflammatory activity elicited by TNFα.
%K Cirugía bariátrica
%K Índice de masa corporal
%K Citocinas
%K Ácidos grasos no esterificados
%K Macrófagos
%K Obesidad
%K Factor de necrosis tumoral alfa
%K Factores de necrosis tumoral
%K Adipocitos
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