科研之友
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摘要
Obesity is associated with a chronic inflammatory state characterized by adipose tissue macrophage infiltration and inflammation, which contributes to insulin resistance. The cholinergic antiinflammatory pathway, which acts through the macrophage alpha 7-nicotinic acetylcholine receptor (alpha 7nAChR), is important in innate immunity. Here we show that adipose tissue possesses a functional cholinergic signaling pathway. Activating this pathway by nicotine in genetically obese (db/db) and diet-induced obese mice significantly improves glucose homeostasis and insulin sensitivity without changes of body weight. This is associated with suppressed adipose tissue inflammation. In addition, macrophages from alpha 7nAChR-/- [alpha 7 knockout (alpha 7KO)] mice have elevated proinflammatory cytokine production in response to free fatty acids and TNF alpha, known agents causing inflammation and insulin resistance. Nicotine significantly suppressed free fatty acid- and TNF alpha-induced cytokine production in wild type (WT), but not alpha 7KO macrophages. These data suggest that alpha 7nAChR is important in mediating the antiinflammatory effect of nicotine. Indeed, inactivating this pathway in alpha 7KO mice results in significantly increased adipose tissue infiltration of classically activated M1 macrophages and inflammation in alpha 7KO mice than their WT littermates. As a result, alpha 7KO mice exhibit more severely impaired insulin sensitivity than WT mice without changes of body weight. These data suggest that the cholinergic antiinflammatory pathway plays an important role in obesity-induced inflammation and insulin resistance. Targeting this pathway may provide novel therapeutic benefits in the prevention and treatment of obesity-induced inflammation and insulin resistance. (Endocrinology 152: 836-846, 2011)
- 出版日期2011-3
