The CSF1 receptor inhibitor pexidartinib (PLX3397) reduces tissue macrophage levels without affecting glucose homeostasis in mice

Int J Obes (Lond). 2020 Jan;44(1):245-253. doi: 10.1038/s41366-019-0355-7. Epub 2019 Mar 29.


Background and objectives: Excessive adipose tissue macrophage accumulation in obesity has been implicated in mediating inflammatory responses that impair glucose homeostasis and promote insulin resistance. Colony-stimulating factor 1 (CSF1) controls macrophage differentiation, and here we sought to determine the effect of a CSF1 receptor inhibitor, PLX3397, on adipose tissue macrophage levels and understand the impact on glucose homeostasis in mice.

Methods: A Ten-week-old mice were fed a chow or high-fat diet for 10 weeks and then treated with PLX3397 via oral gavage (50 mg/kg) every second day for 3 weeks, with subsequent monitoring of glucose tolerance, insulin sensitivity and assessment of adipose tissue immune cells.

Results: PLX3397 treatment substantially reduced macrophage numbers in adipose tissue of both chow and high-fat diet fed mice without affecting total myeloid cell levels. Despite this, PLX3397 did not greatly alter glucose homeostasis, did not affect high-fat diet-induced increases in visceral fat cytokine expression (Il-6 and Tnfa) and had limited effect on the phosphorylation of the stress kinases JNK and ERK and macrophage polarization.

Conclusions: Our results indicate that macrophage infiltration of adipose tissue induced by a high-fat diet may not be the trigger for impairments in whole body glucose homeostasis, and that anti-CSF1 therapies are not likely to be useful as treatments for insulin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue* / cytology
  • Adipose Tissue* / drug effects
  • Aminopyridines / pharmacology*
  • Animals
  • Diet, High-Fat
  • Glucose / metabolism*
  • Homeostasis / drug effects
  • Insulin Resistance / physiology*
  • Macrophages / drug effects*
  • Mice
  • Obesity
  • Pyrroles / pharmacology*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors


  • Aminopyridines
  • Csf1r protein, mouse
  • Pyrroles
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • pexidartinib
  • Glucose