Macrophages, inflammation, and insulin resistance.
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.
Department of Medicine, University of California-San Diego, La Jolla, CA 92093-0651, USA. jolefsky@ucsd.edu
Jerrold M
JM
Olefsky
Christopher K
CK
Glass
D000273:Adipose Tissue / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000473:pathology; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000473:pathology; D009765:Obesity / Q000503:physiopathology; D047495:PPAR gamma / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology
D000893:Anti-Inflammatory Agents; D017127:Glycation End Products, Advanced; D047495:PPAR gamma; D051197:Toll-Like Receptor 4