Session: OR15-Adipokine Action
Room 303 (Moscone Center)
Results: Expression of PAPP-A mRNA and protein was significantly higher in human preadipocytes from Om compared to Sc fat depots. Proinflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor -α (TNF-α), significantly stimulated PAPP-A mRNA and protein expression in preadipocytes through nuclear factor (NF) kB, c-Jun N-terminal kinase (JNK) and p38 pathways. IL-1β appeared to stimulate PAPP-A expression through the JNK pathway more effectively than TNF-α. No effect on phosphatidylinositol 3-kinase or Erk1/2 pathways was seen with these cytokines. Pretreatment of preadipocytes with resveratrol markedly inhibited cytokine-stimulated PAPP-A expression. This down-regulation of PAPP-A by resveratrol did not occur through known targets of resveratrol, i.e., AMP kinase or SIRT1.
Summary and Conclusions: PAPP-A is preferentially expressed in human preadipocytes from visceral fat and is up-regulated by inflammatory cytokines. The intracellular pathways mediating PAPP-A up-regulation are commonly associated with stress, including JNK, p38 and NFkB, although IL-1β and TNF-α seem to have differing effects. Resveratrol down-regulates cytokine-induced PAPP-A expression through a pathway that appears to be independent of SIRT1 and AMPK. These data position PAPP-A as an important regulator of depot-specific adipogenesis with implications for potential treatment and/or prevention strategies for obesity and obesity-related disease.
Nothing to Disclose: CJD, CJE, CAC
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