Cold-Induced Browning Dynamically Alters the Expression Profiles of Inflammatory Adipokines with Tissue Specificity in Mice

Int J Mol Sci. 2016 May 23;17(5):795. doi: 10.3390/ijms17050795.


Cold exposure or β₃-adrenoceptor agonist treatment induces the adipose tissues remodeling, relevant for beige adipogenesis within white adipose tissue (WAT). It remains unclear whether this process influences inflammatory adipokines expression in adipose tissues. We determine the temporal profile of cold or β₃-adrenoceptor agonist (CL316,243)-induced changes in the expression of inflammatory adipokines in adipose tissues in mice or primary mice adipocytes. Male C57BL/6J mice at eight weeks old were exposed to 4 °C for 1-5 days. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous WAT (sWAT) and epididymal WAT (eWAT) were harvested for gene and protein expression analysis. In addition, cultured primary mice brown adipocyte (BA) and white adipocyte (WA) treated with or without CL316,243 were harvested for gene expression analysis. The inflammatory adipokines expressed significantly higher in WAT than BAT at baseline. They were rapidly changed in iBAT, while down-regulated in sWAT and up-regulated in eWAT during the cold acclimation. Upon CL316,243 treatment, detected inflammatory adipokines except Leptin were transiently increased in both BA and WA. Our in vivo and in vitro data demonstrate that the browning process alters the inflammatory adipokines expression in adipose tissues, which is acutely responded to in iBAT, dynamically decreased in sWAT whilst increased in eWAT for compensation.

Keywords: beige cells; cold exposure; depot-specificity; inflammatory adipokines; β3-adrenoceptor agonist.

MeSH terms

  • Adipocytes, Brown / cytology
  • Adipocytes, Brown / metabolism
  • Adipocytes, White / cytology
  • Adipocytes, White / metabolism
  • Adipokines / genetics*
  • Adipokines / metabolism*
  • Adipose Tissue, Brown / metabolism*
  • Adrenergic beta-3 Receptor Agonists / pharmacology*
  • Animals
  • Cells, Cultured
  • Cold Temperature
  • Dioxoles / pharmacology*
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organ Specificity
  • Stress, Physiological* / drug effects


  • Adipokines
  • Adrenergic beta-3 Receptor Agonists
  • Dioxoles
  • disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate