RT Journal Article T1 The rise of soluble TWEAK levels in severely obese subjects after bariatric surgery may affect adipocyte-cytokine production induced by TNFα. A1 Maymó-Masip, Elsa A1 Fernández-Veledo, Sonia A1 García España, Antonio A1 Vázquez-Carballo, Ana A1 Tinahones, Francisco José A1 García-Fuentes, Eduardo A1 Garrifo-Sánchez, Lourdes A1 Rodríguez, María del Mar A1 Vendrell, Joan A1 Chacón, Matilde R K1 Cirugía bariátrica K1 Índice de masa corporal K1 Citocinas K1 Ácidos grasos no esterificados K1 Macrófagos K1 Obesidad K1 Factor de necrosis tumoral alfa K1 Factores de necrosis tumoral K1 Adipocitos AB 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. PB Endocrine Society SN 0021-972X YR 2013 FD 2013-08 LK http://hdl.handle.net/10668/1695 UL http://hdl.handle.net/10668/1695 LA en NO Maymó-Masip E, Fernández-Veledo S, García España A, Vázquez-Carballo A, Tinahones FJ, García-Fuentes E, et al. The rise of soluble TWEAK levels in severely obese subjects after bariatric surgery may affect adipocyte-cytokine production induced by TNFα. J Clin Endocrinol Metab. 2013; 98(8):E1323-33 NO Journal Article; Research Support, Non-U.S. Gov't; DS RISalud RD Apr 7, 2025