Journal Article

Alterations of nitric oxide homeostasis as trigger of intestinal barrier dysfunction in non‐alcoholic fatty liver disease

Trauner, Michael, Staufer, Katharina, Rajcic, Dragana, Staltner, Raphaela, Baumann, Anja, Jung, Finn, Sánchez, Victor, Brandt, Annette, Nier, Anika, Bergheim, Ina

2022

Overview

Changes in intestinal nitric oxide metabolism are discussed to contribute for the development of intestinal barrier dysfunction in non‐alcoholic fatty liver disease (NAFLD). To induce steatosis, female C57BL/6J mice were pair‐fed with a liquid control diet (C) or a fat‐, fructose‐ and cholesterol‐rich diet (FFC) for 8 weeks. Mice received the diets ± 2.49 g L‐arginine/kg bw/day for additional 5 weeks. Furthermore, mice fed C or FFC ± L‐arginine/kg bw/day for 8 weeks were concomitantly treated with the arginase inhibitor Nω‐hydroxy‐nor‐L‐arginine (nor‐NOHA, 0.01 g/kg bw). Liver damage, intestinal barrier function, nitric oxide levels and arginase activity in small intestine were assessed. Also, arginase activity was measured in serum from 13 patients with steatosis (NAFL) and 14 controls. The development of steatosis with beginning inflammation was associated with impaired intestinal barrier function, increased nitric oxide levels and a loss of arginase activity in small intestine in mice. L‐arginine supplementation abolished the latter along with an improvement of intestinal barrier dysfunction; nor‐NOHA attenuated these effects. In patients with NAFL, arginase activity in serum was significantly lower than in healthy controls. Our data suggest that increased formation of nitric oxide and a loss of intestinal arginase activity is critical in NAFLD‐associated intestinal barrier dysfunction.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Animals / Arginase / arginase activity / Arginine / Arginine - metabolism / Arginine - pharmacology / Carbohydrates / Cholesterol / Diet / endotoxin / Fatty liver / Female / Homeostasis / Humans / intestinal barrier function / Laboratory animals / Liver - metabolism / Liver diseases / L‐arginine / Mice / Mice, Inbred C57BL / Nitric oxide / Nitric Oxide - metabolism / Non-alcoholic Fatty Liver Disease - etiology / Non-alcoholic Fatty Liver Disease - metabolism / non‐alcoholic steatohepatitis / Original / Permeability / Plasma / Small intestine / Steatosis / Toll-Like Receptor 4 - metabolism