CXCL3 positively regulates adipogenic differentiation

J Lipid Res. 2016 Oct;57(10):1806-1820. doi: 10.1194/jlr.M067207. Epub 2016 Aug 10.


Chemokines are a family of cytokines inducing cell migration and inflammation. Recent reports have implicated the roles of chemokines in cell differentiation. However, little is known about the functional roles of chemokines in adipocytes. Here, we explored gene expression levels of chemokines and chemokine receptors during adipogenic differentiation. We have found that two chemokines, chemokine (C-X-C motif) ligand 3 (CXCL3) and CXCL13, as well as CXC chemokine receptor 2 (CXCR2), a CXCL3 receptor, are highly expressed in mature adipocytes. When 3T3-L1 cells and ST2 cells were induced to differentiate, both the number of lipid droplets and the expression levels of adipogenic markers were significantly promoted by the addition of CXCL3, but not CXCL13. Conversely, gene knockdown of either CXCL3 or CXCR2 by specific siRNA effectively inhibited the course of adipogenic differentiation. CXCL3 treatment of 3T3-L1 cells significantly induced the phosphorylation of ERK and c-jun N-terminal kinase (JNK). Furthermore, CXCL3-induced CCAAT-enhancer binding protein (C/EBP)β and δ expression was suppressed by both ERK and JNK-specific inhibitors. Furthermore, chromatin immunoprecipitation assay revealed functional binding of PPARγ2 within the cxcl3 promoter region. Taken together, these results have indicated that CXCL3 is a novel adipokine that facilitates adipogenesis in an autocrine and/or a paracrine manner through induction of c/ebpb and c/ebpd.

Keywords: C-X-C motif chemokine ligand 3; adipocytes; chemokine; cytokines; inflammation; peroxisome proliferator-activated receptors; protein kinases/mitogen-activated protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis / physiology*
  • Adipokines / biosynthesis*
  • Adipokines / genetics
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • CCAAT-Enhancer-Binding Protein-delta / genetics
  • CCAAT-Enhancer-Binding Protein-delta / metabolism
  • Cell Differentiation / physiology*
  • Chemokine CXCL13 / genetics
  • Chemokine CXCL13 / metabolism
  • Chemokines, CXC / biosynthesis*
  • Chemokines, CXC / genetics
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System / physiology*
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Paracrine Communication / physiology*
  • Promoter Regions, Genetic
  • Receptors, Interleukin-8B / genetics
  • Receptors, Interleukin-8B / metabolism


  • Adipokines
  • CCAAT-Enhancer-Binding Protein-beta
  • Cebpb protein, mouse
  • Cebpd protein, mouse
  • Chemokine CXCL13
  • Chemokines, CXC
  • Cxcl13 protein, mouse
  • Cxcl3 protein, mouse
  • PPAR gamma
  • Receptors, Interleukin-8B
  • CCAAT-Enhancer-Binding Protein-delta
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases