Non-alcoholic 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 high-fat diet (HFD) feeding for 16 weeks in wild-type and mucin-2 knockout mice. Muc2 deficiency protected mice from HFD-induced fatty liver disease and obesity. Muc2 knockout mice exhibited a better glucose homeostasis, reduced inflammation, upregulated expression of genes involved in lipolysis and fatty acid β-oxidation in the white adipose tissue compared with wild-type mice after 16 weeks of HFD feeding. They also displayed increased intestinal and plasma levels of interleukin-22 (IL-22), and higher intestinal levels of the IL-22 target genes Reg3b and Reg3g compared with wild-type mice fed HFD. Our findings indicate that absence of the intestinal mucus layer activates the mucosal immune system. Increased IL-22 levels protect mice from diet-induced features of the metabolic syndrome.
- metabolic syndrome
- Copyright © 2015, American Journal of Physiology- Gastrointestinal and Liver Physiology