Abstract 16633: Differential Effects of Acute and Chronic Inflammation on the Release of Adiponectin By Human Adipose Tissue
Background: Adiponectin (Adpn) is an anti-inflammatory adipokine. In cell culture studies, pro-inflammatory cytokines suppress adiponectin’s biosynthesis, however in clinical studies adiponectin levels are increased in patients with high background inflammation. We explored the effects of acute and chronic inflammation on adiponectin’s release by human adipose tissue (AT).
Methods: In Study 1, 19 healthy subjects were randomized to receive S.typhii vaccine or placebo, as a model of acute in-vivo inflammation. Blood samples were obtained at baseline and at 8h, 12h and 24h post vaccination to measure serum Adpn and interleukin-6 (IL-6) by ELISA. In Study 2, mesothoracic AT from 6 patients undergoing coronary artery bypass grafting (CABG) operation was cultured ex-vivo for 24h +/- IL-6 (25ng/mL) and tumor necrosis factor-a (TNF-a, 4ng/mL). In Study 3 subcutaneous, mesothoracic and gluteal AT samples from 110 patients undergoing CABG were cultured ex-vivo for 4h, and the release of Adpn and IL-6 was determined in AT supernatants.
Results: In Study 1 acute inflammation in-vivo increased IL-6 (A) and reduced Adpn levels at 24h (B). In Study 2 incubation of mesothoracic AT with IL-6/TNF-a for 24h suppressed Adpn release in AT supernatants at 24h (C). In Study 3 the release of IL-6 by subcutaneous, mesothoracic and gluteal AT was positively correlated with the release of Adpn by the same AT depots (D).
Conclusions: By using both an in-vivo and an ex-vivo model of acute inflammation we demonstrated that acute inflammation suppresses the release of Adpn from human AT and reduces circulating Adpn levels. On the contrary atherosclerosis-related, low-grade chronic inflammation increases the release of Adpn by human AT, possibly as a counter-regulatory defence mechanism. These novel findings provide new insights into the complex mechanisms regulating adiponectin’s biosynthesis in human adipose tissue.
- © 2012 by American Heart Association, Inc.