Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Int J Obes (Lond). 2005 Nov;29(11):1299-307. doi: 10.1038/sj.ijo.0803032.


Background: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment during inflammation whose plasma level is elevated in obesity.

Objective: The present studies were designed to examine the release of MCP-1 in primary culture by explants of visceral adipose tissue from morbidly obese women.

Results: Most of the MCP-1 released by adipose tissue explants was derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose tissue explants was upregulated almost five-fold between 3 and 48 h of incubation. Approximately half of this upregulation was due to the release of endogenous tumor necrosis factor alpha (TNFalpha) and IL-1beta based on the ability of a combination of a soluble TNFalpha receptor (etanercept) and a blocking antibody against IL-1beta to reduce MCP-1 release. The release of MCP-1 over 48 h was unaffected by insulin or dexamethasone but significantly reduced by the combination of both agents. MCP-1 release was reduced by 60% in the presence of an inhibitor of the nuclear factor kappaB (NF-kappaB) pathway. There were no significant effects of inhibitors of p44/42 mitogen-activated protein kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the presence of inhibitors of both the p38 MAPK and NF-kappaB pathways was greater than that seen with only the NF-kappaB inhibitor.

Discussion: The present data shows that MCP-1 formation is upregulated over a 48-h incubation of primary explants of visceral adipose tissue. Half of this upregulation is dependent upon endogenous TNFalpha and Il-1beta and involves the p38 MAPK and NF-kappaB pathways.

Publication types

  • Comparative Study

MeSH terms

  • Abdominal Fat / metabolism*
  • Adipocytes / metabolism
  • Adult
  • Antibodies, Monoclonal / pharmacology
  • Chemokine CCL2 / metabolism*
  • Dinoprostone / metabolism
  • Etanercept
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Immunoglobulin G / pharmacology
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Middle Aged
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Receptors, Tumor Necrosis Factor
  • Signal Transduction / physiology*
  • Stromal Cells / metabolism
  • Time Factors
  • Tissue Culture Techniques
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antibodies, Monoclonal
  • Chemokine CCL2
  • Immunoglobulin G
  • Interleukin-1
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Dinoprostone
  • Etanercept