Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity
Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity
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DOI：
10.1152/ajpgi.00094.2015
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发表时间：
2016-03-01
影响因子：
4.5
通讯作者：
Schnabl, Bernd
中科院分区：
文献类型：
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作者：
Hartmann, Phillipp;Seebauer, Caroline T.;Schnabl, Bernd
非酒精性脂肪肝 (NAFLD) 和肥胖的特点是肠道微生物群改变、炎症和肠道屏障功能障碍。在这里，我们研究了粘蛋白-2 (Muc2) 作为肠道粘液层的主要成分在脂肪肝疾病和肥胖发展中的作用。我们研究了通过给野生型和 Muc2 敲除小鼠喂食高脂肪饮食 (HFD) 16 周而诱发的实验性脂肪肝疾病和肥胖。 Muc2 缺乏可以保护小鼠免受 HFD 诱导的脂肪肝疾病和肥胖症的影响。与野生型小鼠相比，经过 16 周的 HFD，Muc2 敲除小鼠表现出更好的葡萄糖稳态、减少的炎症以及白色脂肪组织中参与脂肪分解和脂肪酸 β-氧化的基因表达上调。与同样喂食 HFD 的野生型小鼠相比，Muc2 敲除小鼠还表现出更高的肠道和血浆 IL-22 水平以及更高的 IL-22 靶基因 Reg3b 和 Reg3g 肠道水平。我们的研究结果表明，肠道粘液层的缺失会激活粘膜免疫系统。较高的 IL-22 水平可以保护小鼠免受饮食引起的代谢综合征的影响。
Nonalcoholic fatty liver disease (NAFLD) and obesity are characterized by altered gut microbiota, inflammation, and gut barrier dysfunction. Here, we investigated the role of mucin-2 (Muc2) as the major component of the intestinal mucus layer in the development of fatty liver disease and obesity. We studied experimental fatty liver disease and obesity induced by feeding wild-type and Muc2-knockout mice a high-fat diet (HFD) for 16 wk. Muc2 deficiency protected mice from HFD-induced fatty liver disease and obesity. Compared with wildtype mice, after a 16-wk HFD, Muc2-knockout mice exhibited better glucose homeostasis, reduced inflammation, and upregulated expression of genes involved in lipolysis and fatty acid beta-oxidation in white adipose tissue. Compared with wild-type mice that were fed the HFD as well, Muc2-knockout mice also displayed higher intestinal and plasma levels of IL-22 and higher intestinal levels of the IL-22 target genes Reg3b and Reg3g. Our findings indicate that absence of the intestinal mucus layer activates the mucosal immune system. Higher IL-22 levels protect mice from diet-induced features of the metabolic syndrome.