TNF-[alpha] and adiponectin pathways are deregulated in endometria from obese women with polycystic ovarian syndrome.

Seventy percent of women bearing PCOS are obese; adiponectin and TNFα, as obesity markers, have a dual role in the sensitivity and action of insulin. Adiponectin (insulin sensitising) decreases, whereas, TNFα, IL6 (negative regulators of insulin pathway) increases in obese-women. Moreover, TNFα decreases the transcript and protein levels of adiponectin. These changes could affect the normal energetic status in endometrium, tissue that exhibits abnormal insulin signalling in the PCOS condition (hyperandrogenic/hyperinsulinic environment). The aim of the present work was to evaluate molecules involved in TNFα (RTNFα 1 y 2, NFkB, p-IKK) and adiponectin (AdipoR1, AdipoR2, APPL1, TAK1, MEK1) signalling in endometria (n=15) from lean, Obese and Obese-PCOS women by western-blot, immunohistochemistry and real-time PCR. Also, the number of macrophages was evaluated by CD68 and plasma levels of adiponectin, TNFα and IL-6 were assayed by ELISA. No changes in serum TNF-α levels were observed, however, IL-6 levels increase in both Obese groups vs Lean (P<0.01). Adiponectin was lower in Obese-SOP (P<0.01). TNFα, its receptors and CD68 levels increase in Obese-PCOS vs other groups (P<0.05). Transcripts levels for adiponectin, TNFα/receptors and APPL1 were similar in the three groups of endometria. NFkB nuclear localization was higher in Obese-SOP vs the other groups (P<0.05) and activated IKK increased markedly in both groups of Obese vs Lean group (P<0.0001). Adiponectin protein levels (plasma and endometrial), AdipoR1, APPL1 and MEK1 were low in Obese-PCOS vs Lean group (P<0.05); TAK1 diminished in both Obese endometria (P<0.05). Consequently, there is an increased inflammatory environment in endometrium of Obese-PCOS women that could decrease adiponectin signalling, through the participation of TNFα, NFκB activation and/or IL-6 signalling; therefore, affecting insulin signalling under obesity, hyperandrogenic and hyperinsulinic conditions, compromising the energetic metabolism for normal endometrial function.