Adipokines identified as new downstream targets for adiponectin: lessons from adiponectin-overexpressing or -deficient mice

作者：Ge Qian; Ryken Laurence; Noel Laurence; Maury Eleonore; Brichard Sonia M^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2011, 301(2): E326-E335.

DOI：10.1152/ajpendo.00153.2011

• inflammation
• adipocytes
• stromal-vascular cells
• secretome

Ge Q, Ryken L, Noel L, Maury E, Brichard SM. Adipokines identified as new downstream targets for adiponectin: lessons from adiponectin-overexpressing or -deficient mice. Am J Physiol Endocrinol Metab 301: E326-E335, 2011. First published May 3, 2011; doi:10.1152/ajpendo.00153.2011.-Adipokines play a central role in the pathogenesis of the metabolic syndrome. Among them, adiponectin (ApN), a master regulator of immune and fuel homeostasis, is decreased. Identifying downstream adipokines targeted by ApN may help in deciphering this syndrome. We have generated transgenic mice, allowing persistent and moderate overexpression of ApN (ApN-Overex) specifically in white adipose tissue (AT). We took advantage of this model to unravel the adipokine secretion profile triggered by ApN. AT was fractionated into adipocytes and stromal-vascular cells (SVC), which were cultured for 8 h. Profiling of secretory products by antibody arrays and subsequent ELISAs showed that the secretion of three proinflammatory factors (IL-17B, IL-21, TNF alpha) and three hematopoietic growth factors [GF; thrombopoietin and granulocyte (macrophage) colony-stimulating-factors] was reduced in adipocytes of ApN-Overex mice compared with wild-type mice. In the SVC of these mice, besides the hematopoietic GFs, the secretion of another GF (vascular endothelial GF receptor 1), two chemokines (RANTES and ICAM-1), and two proinflammatory factors (IL-6 and IL-12p70) was reduced as well. Only one cytokine, IL-1 receptor 4, was oversecreted by SVC of ApN-Overex mice, which may exhibit anti-inflammatory properties. Most of these changes in secretion were due to corresponding changes in mRNAs. A reverse profile of adipokine expression was observed in ApN-KO mice. In conclusion, ApN regulates in vivo the secretion of downstream adipokines, thereby inducing a shift of the immune balance in both adipocytes and SVC toward a less inflammatory phenotype. These downstream adipokines may be new therapeutic targets for the management of the metabolic syndrome.

• 出版日期2011-8