Prevention of colitis-induced liver oxidative stress and inflammation in a transgenic mouse model with increased omega-3 polyunsaturated fatty acids
Nadine Rohwer,
Julia Jelleschitz,
Annika Höhn,
Daniela Weber,
Anja A. Kühl,
Chaoxuan Wang,
Rei-Ichi Ohno,
Nadja Kampschulte,
Anne Pietzner,
Nils Helge Schebb,
Karsten-H. Weylandt,
Tilman Grune
Affiliations
Nadine Rohwer
Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology and Diabetes, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, Brandenburg Medical School and University of Potsdam, Potsdam, Germany; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
Julia Jelleschitz
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
Annika Höhn
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany
Daniela Weber
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
Anja A. Kühl
iPATH.Berlin–Immunopathology for Experimental Models, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Chaoxuan Wang
Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology and Diabetes, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, Brandenburg Medical School and University of Potsdam, Potsdam, Germany; Medical Department, Division of Psychosomatic Medicine, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany
Rei-Ichi Ohno
University of Wuppertal, Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, Wuppertal, Germany
Nadja Kampschulte
University of Wuppertal, Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, Wuppertal, Germany
Anne Pietzner
Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology and Diabetes, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, Brandenburg Medical School and University of Potsdam, Potsdam, Germany
Nils Helge Schebb
University of Wuppertal, Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, Wuppertal, Germany
Karsten-H. Weylandt
Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology and Diabetes, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, Brandenburg Medical School and University of Potsdam, Potsdam, Germany
Tilman Grune
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany; Corresponding author. German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114 - 116, 14558, Nuthetal, Germany.
Inflammatory bowel disease (IBD) is an immune-mediated gut dysfunction, which might also be associated with an inflammatory phenotype in the liver. It is known that the nutritional intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) is inversely correlated to the severity and occurrence of IBD. In order to investigate whether n-3 PUFA can also reduce liver inflammation and oxidative liver damage due to colon inflammation, we explored the dextran sulfate sodium (DSS)-induced colitis model in wild-type and fat-1 mice with endogenously increased n-3 PUFA tissue content. Besides confirming previous data of alleviated DSS-induced colitis in the fat-1 mouse model, the increase of n-3 PUFA also resulted in a significant reduction of liver inflammation and oxidative damage in colitis-affected fat-1 mice as compared to wild-type littermates. This was accompanied by a remarkable increase of established inflammation-dampening n-3 PUFA oxylipins, namely docosahexaenoic acid-derived 19,20-epoxydocosapentaenoic acid and eicosapentaenoic acid-derived 15-hydroxyeicosapentaenoic acid and 17,18-epoxyeicosatetraenoic acid. Taken together, these observations demonstrate a strong inverse correlation between the anti-inflammatory lipidome derived from n-3 PUFA and the colitis-triggered inflammatory changes in the liver by reducing oxidative liver stress.
