The role of GM-CSF in adipose tissue inflammation

Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1038-46. doi: 10.1152/ajpendo.00061.2008. Epub 2008 Sep 2.


Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine that has a central action to reduce food intake and body weight. Consistent with this, GM-CSF knockout mice are more obese and hyperphagic than wild-type mice. However, in lung, GM-CSF is an important determinant of macrophage infiltration. Consequently, we sought to determine if GM-CSF might contribute to adipose tissue macrophage accumulation, insulin resistance, and low-grade inflammation that occurs when animals gain weight on a high-fat diet (HFD). We therefore determined how targeted genetic disruption of GM-CSF can affect adipose tissue macrophage and cytokine gene expression as well as glucose homeostasis by performing hyperinsulinemic-euglycemic clamps. The number of macrophages and CCR2 gene expression in adipose tissue of GM-CSF knockout mice was decreased relative to those in wild-type mice, and the adipocyte size of mesenteric fat was increased in GM-CSF knockout mice on a HFD compared with wild-type mice. The level of mRNA of the proinflammatory cytokines interleukin-1beta, tumor necrosis factor-alpha, and macrophage inflammatory protein-1alpha was significantly lower in mesenteric fat of GM-CSF knockout mice on the HFD than in wild-type mice. Using the hyperinsulinemic-euglycemic clamp technique, GM-CSF knockout mice had greater overall insulin sensitivity. This increase was due to enhanced peripheral uptake and utilization of glucose rather than to increased hepatic insulin sensitivity. Collectively, the data suggest that the GM-CSF knockout mutation ameliorates peripheral insulin resistance in spite of increased adiposity by reducing inflammation in adipose tissue in response to a HFD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism*
  • Adipose Tissue, White / pathology
  • Animals
  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Body Weight / genetics
  • Body Weight / physiology
  • Cell Count
  • Chemokine CCL2 / genetics
  • Chemokine CCL3 / genetics
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology
  • Gene Expression / drug effects
  • Glucose Clamp Technique
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Insulin / blood
  • Interleukin-1beta / genetics
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mesentery / drug effects
  • Mesentery / metabolism
  • Mesentery / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CCR2 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / genetics


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Blood Glucose
  • CD68 protein, mouse
  • Ccl2 protein, mouse
  • Ccl3 protein, mouse
  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL3
  • Dietary Fats
  • Insulin
  • Interleukin-1beta
  • Receptors, CCR2
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor