Macrophage-secreted factors induce adipocyte inflammation and insulin resistance

Biochem Biophys Res Commun. 2006 Mar 10;341(2):507-14. doi: 10.1016/j.bbrc.2006.01.012. Epub 2006 Jan 13.


Macrophage infiltration into adipose tissue increases with obesity, a condition associated with low-grade inflammation and insulin resistance. We investigated the direct effects of macrophage-secreted factors on adipocyte inflammation and insulin resistance. 3T3-L1 adipocytes incubated with media conditioned by RAW264.7 macrophages (RAW-CM) showed dramatically increased transcription of several inflammation-related genes, greater nuclear factor kappa B (NF-kappaB) activity, and enhanced binding of U937 monocytes. All of these effects were prevented by co-incubation with pyrrolidinedithiocarbamate, an NF-kappaB inhibitor. Adipocytes incubated with RAW-CM also released more non-esterified fatty acids and this increased lipolysis was not suppressed by insulin. In addition, RAW-CM treatment decreased insulin-stimulated glucose uptake in adipocytes. Taken together, these results indicate that macrophage-secreted factors induce inflammatory responses and reduce insulin responsiveness in adipocytes. These effects of macrophage-secreted factors on adipocytes may contribute significantly to the systemic inflammation and insulin resistance associated with obesity.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Animals
  • Cell Line
  • Chemokine CCL2 / metabolism
  • Cytokines / metabolism
  • Glucose / metabolism
  • Glucose / pharmacokinetics
  • Humans
  • Inflammation / metabolism
  • Insulin / metabolism
  • Insulin Resistance
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / metabolism
  • Macrophages / metabolism*
  • Mice
  • Models, Statistical
  • NF-kappa B / metabolism
  • Obesity / metabolism
  • Pyrrolidines / pharmacology
  • RNA / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiocarbamates / pharmacology
  • Time Factors
  • U937 Cells


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Cytokines
  • Insulin
  • Interleukin-6
  • NF-kappa B
  • Pyrrolidines
  • Thiocarbamates
  • Intercellular Adhesion Molecule-1
  • pyrrolidine dithiocarbamic acid
  • RNA
  • Glucose