RESUMEN
BACKGROUND: Chronically elevated interleukin-6 (IL-6) is implicated in obesity-associated pathologies, where a proportion of this cytokine is derived from adipose tissue. Proinflammatory prostaglandins, which regulate this cytokine elsewhere, are also produced by this tissue. OBJECTIVE: To investigate whether constitutively active cyclooxygenase (COX)/prostaglandin (PG) pathway in white adipose tissue (WAT) is responsible for basal IL-6 production. DESIGN: The effect of acetylsalicylic acid (ASA), an inhibitor of COX, on IL-6 was assessed in human subjects and mice. COX, downstream PG synthase (PGS) activity and PG receptor signalling were determined in subcutaneous (SC), gonadal (GN) WAT and adipocytes. METHODS AND RESULTS: In obese humans, low-dose ASA (150 mg day(-1) for 10 days) inhibited systemic IL-6 and reduced IL-6 release from SC WAT ex vivo (0.2 mM). Similarly, in mice, ASA (0.2 and 2.0 mg kg(-1)) suppressed SC WAT 6-keto-PGF(1alpha) (a stable metabolite of prostacyclin) and IL-6 release. Although both COX isoforms are comparably expressed, prostacyclin synthase expression is higher in GN WAT, with levels of activity correlating directly with IL-6. Both ASA (5 mM) and NS-398 (COX-2 selective inhibitor Asunto(s)
Tejido Adiposo Blanco/metabolismo
, Aspirina/administración & dosificación
, Inhibidores de la Ciclooxigenasa/administración & dosificación
, Interleucina-6/metabolismo
, Obesidad/metabolismo
, Adipocitos/metabolismo
, Anciano
, Animales
, Aspirina/farmacología
, Estudios de Casos y Controles
, Inhibidores de la Ciclooxigenasa/farmacología
, Femenino
, Gónadas/metabolismo
, Humanos
, Masculino
, Ratones
, Ratones Obesos
, Persona de Mediana Edad
, Prostaglandina-Endoperóxido Sintasas/metabolismo
, Receptores de Prostaglandina/metabolismo
, Grasa Subcutánea/metabolismo
, Factor de Necrosis Tumoral alfa/sangre