Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-κB, peroxisomal proliferator-activated receptor-γ and extracellularly regulated kinase 1/2

Beyond their effects on central metabolic functions, leptin, resistin, and adiponectin have profound effects on a number of other physiologic processes, including immune function and inflammation. Although leptin, resistin, and adiponectin are produced in human placenta and adipose tissue, their immunoregulatory actions in these tissues are not known. Therefore, the aim of this study was to determine the effect of leptin, resistin, and adiponectin on the release of proinflammatory mediators in human placenta and sc adipose tissue. Samples were obtained from normal pregnancies at the time of cesarean section. Tissue explants (n = 5) were incubated in the absence ( basal control) or presence of a leptin ( 1, 10, and 100 ng/ml), resistin ( 1, 10, and 100 ng/ml), and adiponectin (0.1 and 0.5 mu g/ml). After 6 h incubation, the medium was collected, and the release of IL-1 beta, IL-6, TNF alpha, prostaglandin ( PG) F-2 alpha and PGE(2) was quantified by ELISA. There was no effect of resistin on proinflammatory cytokine or prostaglandin release; and/or 0.5 mu g/ml significantly increased the release of IL-1 beta, IL-6, TNF alpha, and PGE(2) from human placenta and adipose tissue. Although both leptin and adiponectin significantly increased PGF(2 alpha) release from human placenta, there was no effect of these hormones on PGF(2 alpha) release from adipose tissue. Furthermore, this leptin- and adiponectin-induced proinflammatory response could be abrogated by treatment with the antiinflammatory ERK1/2 MAPK inhibitor U0126, the peroxisomal proliferator-activated receptor-gamma ligand troglitazone, and the nuclear factor-kappa B inhibitor BAY 11-7082. Collectively, these data indicate that leptin and adiponectin activate proinflammatory cytokine release and phospholipid metabolism in human placenta and adipose tissue, and antiinflammatory agents can abrogate leptin- and adiponectin-induced inflammation.