Effects of methotrexate on inflammatory alterations induced by obesity: an in vivo and in vitro study

Mol Cell Endocrinol. 2012 Sep 25;361(1-2):92-8. doi: 10.1016/j.mce.2012.03.016. Epub 2012 Mar 29.


Immunosuppressant drugs, such as methotrexate, are able to inhibit cytokine production and leukocyte migration to inflammatory foci; therefore, they could modify the establishment of inflammation in adipose tissue during obesity. Thus, we studied the effects of methotrexate in vivo on high-fat diet induced-obesity in mice and in vitro in isolated and co-cultured adipocytes and macrophages. Obese mice treated with methotrexate presented reduced serum levels of TNF-α, insulin and glucose, and an improvement of insulin sensitivity. Adipose tissue from these mice produced less proinflammatory (TNF-α, IL-6, leptin) and more anti-inflammatory adipokines (adiponectin and IL-10) associated with reduced macrophage infiltration and inflammation. Cytokine inhibition was also confirmed in isolated and co-cultured adipocytes and macrophages. Methotrexate presented anti-lipolytic effect in vivo and, in vitro through adenosine release. Drugs that combine anti-lipolytic effect and the ability to control inflammation in adipose tissue could play a role in the control of insulin resistance and other pathologies associated with obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adipose Tissue / drug effects
  • Adipose Tissue / pathology
  • Adiposity / drug effects
  • Animals
  • Body Weight / drug effects
  • Coculture Techniques
  • Cytokines / blood
  • Cytokines / metabolism
  • Diet, High-Fat
  • Epididymis / drug effects
  • Epididymis / metabolism
  • Epididymis / pathology
  • Inflammation / complications*
  • Inflammation / metabolism
  • Inflammation / pathology*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipolysis / drug effects
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Methotrexate / pharmacology*
  • Mice
  • Nitric Oxide Synthase Type II / metabolism
  • Obesity / complications*
  • Obesity / metabolism
  • Obesity / pathology*
  • Phosphorylation / drug effects


  • Cytokines
  • Nitric Oxide Synthase Type II
  • JNK Mitogen-Activated Protein Kinases
  • Methotrexate