RT Journal Article
T1 Tumor necrosis-like weak inducer of apoptosis as a proinflammatory cytokine in human adipocyte cells: up-regulation in severe obesity is mediated by inflammation but not hypoxia.
A1 Vendrell, Joan
A1 Maymó-Masip, Elsa
A1 Tinahones, Francisco J
A1 García-España, Antonio
A1 Megía, Ana
A1 Caubet, Enric
A1 García-Fuentes, Eduardo
A1 Chacón, Matilde R
K1 TNFSF12 protein, human
K1 TWEAK receptor
K1 Tejido Adiposo
K1 Biopsia
K1 Western Blotting
K1 Línea Celular
K1 Estudios de Cohortes
K1 Citocinas
K1 Diabetes Mellitus Tipo 2
K1 Retículo Endoplásmico
K1 Expresión Génica
K1 Inflamación
K1 Macrófagos
K1 Obesidad Mórbida
K1 Receptores del Factor de Necrosis Tumoral
K1 Transducción de Señal
K1 Factores de Necrosis Tumoral
K1 Regulación hacia Arriba
K1 Adipocitos
K1 Anoxia
AB CONTEXTAdipose tissue hypoxia and endoplasmic reticulum (ER) stress may link the presence of chronic inflammation and macrophage infiltration in severely obese subjects. We previously reported the up-regulation of TNF-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in adipose tissue of severely obese type 2 diabetic subjects.OBJECTIVESThe objective of the study was to examine TWEAK and Fn14 adipose tissue expression in obesity, severe obesity, and type 2 diabetes in relation to hypoxia and ER stress.DESIGNIn the obesity study, 19 lean, 28 overweight, and 15 obese nondiabetic subjects were studied. In the severe obesity study, 23 severely obese and 35 control subjects were studied. In the type 2 diabetes study, 11 type 2 diabetic and 36 control subjects were studied. The expression levels of the following genes were analyzed in paired samples of sc and visceral adipose tissue: Fn14, TWEAK, VISFATIN, HYOU1, FIAF, HIF-1a, VEGF, GLUT-1, GRP78, and XBP-1. The effect of hypoxia, inflammation, and ER stress on the expression of TWEAK and Fn14 was examined in human adipocyte and macrophage cell lines.RESULTSUp-regulation of TWEAK/Fn14 and hypoxia and ER stress surrogate gene expression was observed in sc and visceral adipose tissue only in our severely obese cohort. Hypoxia modulates TWEAK or Fn14 expression in neither adipocytes nor macrophages. On the contrary, inflammation up-regulated TWEAK in macrophages and Fn14 expression in adipocytes. Moreover, TWEAK had a proinflammatory effect in adipocytes mediated by the nuclear factor-kappaB and ERK but not JNK signaling pathways.CONCLUSIONSOur data suggest that TWEAK acts as a pro-inflammatory cytokine in the adipose tissue and that inflammation, but not hypoxia, may be behind its up-regulation in severe obesity.
PB The Endocrine Society
SN 0021-972X
YR 2010
FD 2010-06
LK http://hdl.handle.net/10668/750
UL http://hdl.handle.net/10668/750
LA en
NO Vendrell J, Maymó-Masip E, Tinahones Madueño FJ, García-España A, Megía A, Caubet E, et al. Tumor necrosis-like weak inducer of apoptosis as a proinflammatory cytokine in human adipocyte cells: up-regulation in severe obesity is mediated by inflammation but not hypoxia. J. Clin. Endocrinol. Metab.. 2010; 95(6):2983-92
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 6, 2025