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