Macrophages, Inflammation, and Insulin Resistance

Annu Rev Physiol. 2010;72:219-46. doi: 10.1146/annurev-physiol-021909-135846.

Abstract

Obesity induces an insulin-resistant state in adipose tissue, liver, and muscle and is a strong risk factor for the development of type 2 diabetes mellitus. Insulin resistance in the setting of obesity results from a combination of altered functions of insulin target cells and the accumulation of macrophages that secrete proinflammatory mediators. At the molecular level, insulin resistance is promoted by a transition in macrophage polarization from an alternative M2 activation state maintained by STAT6 and PPARs to a classical M1 activation state driven by NF-kappaB, AP1, and other signal-dependent transcription factors that play crucial roles in innate immunity. Strategies focused on inhibiting the inflammation/insulin resistance axis that otherwise preserve essential innate immune functions may hold promise for therapeutic intervention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipose Tissue / pathology
  • Adipose Tissue / physiopathology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Glycation End Products, Advanced / metabolism
  • Glycation End Products, Advanced / physiology
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology*
  • Inflammation / physiopathology
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology*
  • Liver / pathology
  • Macrophage Activation / physiology
  • Macrophages / physiology*
  • Mice
  • Mice, Transgenic
  • Muscle, Skeletal / pathology
  • Obesity / physiopathology
  • PPAR gamma / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Toll-Like Receptor 4 / physiology

Substances

  • Anti-Inflammatory Agents
  • Glycation End Products, Advanced
  • PPAR gamma
  • Toll-Like Receptor 4