title: Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity.
abstract: 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 wild-type 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 β-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.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California;
authors.forename: Phillipp
authors.initials: P
authors.lastname: Hartmann
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California;
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Seebauer
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California;
authors.forename: Magdalena
authors.initials: M
authors.lastname: Mazagova
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California;
authors.forename: Angela
authors.initials: A
authors.lastname: Horvath
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California; Department of Medicine, VA San Diego Healthcare System, San Diego, California;
authors.forename: Lirui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California; Department of Medicine, VA San Diego Healthcare System, San Diego, California;
authors.forename: Cristina
authors.initials: C
authors.lastname: Llorente
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California; Department of Pathology, University of California San Diego, La Jolla, California; and.
authors.forename: Nissi M
authors.initials: NM
authors.lastname: Varki
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California.
authors.forename: Katharina
authors.initials: K
authors.lastname: Brandl
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California; Department of Medicine, VA San Diego Healthcare System, San Diego, California;
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Ho
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California; Department of Medicine, VA San Diego Healthcare System, San Diego, California; beschnabl@ucsd.edu.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schnabl
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004731:Endotoxins / Q000276:immunology*; D000069196:Gastrointestinal Microbiome; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007378:Interleukins / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D055262:Mucin-2 / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D000073718:Pancreatitis-Associated Proteins; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D012038:Regeneration / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D004731:Endotoxins; D007378:Interleukins; D055262:Mucin-2; D000073718:Pancreatitis-Associated Proteins; D020011:Protective Agents; D011506:Proteins; D000097043:Interleukin-22; C490253:Reg3b protein, mouse; C490255:Reg3g protein, mouse
keywords: Reg3; endotoxin; metabolic syndrome; microbiome