Regulation of Obesity-Related Insulin Resistance with Gut Anti-inflammatory Agents
Regulation of Obesity-Related Insulin Resistance with Gut Anti-inflammatory Agents
复制标题
用肠道抗炎药调节肥胖相关的胰岛素抵抗
DOI：
10.1016/j.cmet.2015.03.001
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发表时间：
2015-04-07
期刊：
影响因子：
29
通讯作者：
Winer, Daniel A.
中科院分区：
文献类型：
--
作者：
Luck, Helen;Tsai, Sue;Winer, Daniel A.
Obesity has reached epidemic proportions, but little is known about its influence on the intestinal immune system. Here we show that the gut immune system is altered during high-fat diet (HFD) feeding and is a functional regulator of obesity-related insulin resistance (IR) that can be exploited therapeutically. Obesity induces a chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations. Reduction of the gut immune system, using beta7 integrin-deficient mice (Beta7 null), decreases HFD-induced IR. Treatment of wild-type HFD C57BL/6 mice with the local gut anti-inflammatory, 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters. These beneficial effects are dependent on adaptive and gut immunity and are associated with reduced gut permeability and endotoxemia, decreased visceral adipose tissue inflammation, and improved antigen-specific tolerance to luminal antigens. Thus, the mucosal immune system affects multiple pathways associated with systemic IR and represents a novel therapeutic target in this disease.
