Role of cholinergic anti-inflammatory pathway in obesity-mediated insulin resistance
Obesity is related to many diseases,such as diabetes,hypertension,angina pectoris and arthritis,and has become an increasingly serious global public health problem.Chronic low-grade inflammation and activation of immune system are involved in pathogenesis of obesity-related insulin resistance.Insulin is only hormone that can lower blood sugar,and works through insulin signaling pathway.Under normal circumstances,interaction of pro-inflammatory and anti-inflammatory system maintains immune homeostasis.Dynamic balance of pro-inflammatory and anti-inflammatory reactions determines occurrence,development and outcome of inflamma-tion.Activation of inflammatory signaling pathways can induce insulin resistance in central and peripheral tissues,and Toll-like recep-tor 4(TLR4)signaling pathway is one of important pathways that produce pro-inflammatory responses.It has known high-fat diet is associated with chronic low-grade inflammation,which may due to saturated fatty acids activate TLR4 receptors,stimulate expression of inflammatory cytokines,and inhibit insulin signal transduction.In anti-inflammatory system,cholinergic anti-inflammatory pathway(CAP)is a neuroimmunological regulation pathway,which is fast,reversible,accurate and can adapt to changes in inflammatory input signals,which is mainly composed of vagus nerve,spleen and splenic sympathetic nerve,acetylcholine and α7 nicotinic acetyl-choline receptor(α7nAChR).Activation of CAP can improve obesity-induced inflammation and insulin resistance.This review focus on obesity-mediated inflammation,CAP anti-inflammatory pathways,and their relationship with insulin resistance,in order to enrich molecular immune mechanism of insulin resistance,and provide a basis for research of anti-inflammatory diagnosis and treatment of insulin resistance-related diseases.
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