Cathrin Sellmann1, Anja Baumann2, Annette Brandt2, Cheng Jun Jin1, Anika Nier2, Ina Bergheim3,2. 1. Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany; and. 2. Molecular Nutritional Science Division, Department of Nutritional Sciences, University of Vienna, Vienna, Austria. 3. Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany; and ina.bergheim@univie.ac.at.
Abstract
Background: Universally accepted therapeutic strategies for the treatment of nonalcoholic steatohepatitis (NASH) are still lacking. Studies suggest a preventive effect of oral Gln supplementation on the development of NASH; however, whether Gln also has therapeutic potential for pre-existing NASH has not yet been clarified.Objective: The aim of the present study was to determine whether Gln prevents the progression of diet-induced NASH in mice. Methods: For 8 wk, female C57BL/6J mice (6-8 wk old) were pair-fed a liquid Western-style diet [WSD, 25% of energy from fat, 50% wt:wt fructose, 0.16% wt:wt cholesterol] or control diet (C diet) to induce liver damage. From week 8 to 13, they were pair-fed the C diet or WSD alone or supplemented with l-Gln to provide 2.1 g/kg body weight (C diet + Gln or WSD + Gln). Energy intake was adjusted to the group with the lowest energy intake. Indexes of liver damage and inflammation, intestinal barrier function, and toll-like receptor 4 (Tlr4) signaling in the liver were determined. Results: The liver histology scores significantly increased from 8 to 13 wk (+31%) in WSD-fed mice and were significantly higher than in controls (P ≤ 0.05 for both time comparisons), whereas scores did not differ between C diet-fed and WSD + Gln-fed mice after 13 wk of feeding. The occludin protein concentrations in the small intestinal tissue were similarly reduced in both WSD-fed groups when compared with controls [WSD compared with C diet (-53%) and C diet + Gln (-42%), P ≤ 0.05; WSD + Gln compared with C diet + Gln (-34%), P ≤ 0.05] after 13 wk, whereas the expression of myeloid differentiation primary response gene 88 mRNA and concentration of inducible nitric oxide synthase and 4-hydroxynonenal protein adducts were significantly higher only in livers of WSD-fed mice (P ≤ 0.05 for the WSD group compared with all other groups; WSD + Gln group compared with the C diet groups: NS). Conclusion: Taken together, our data suggest that oral Gln supplementation protects mice from the progression of pre-existing, WSD-induced NASH.
Background: Universally accepted therapeutic strategies for the treatment of nonalcoholic steatohepatitis (NASH) are still lacking. Studies suggest a preventive effect of oral Gln supplementation on the development of NASH; however, whether Gln also has therapeutic potential for pre-existing NASH has not yet been clarified.Objective: The aim of the present study was to determine whether Gln prevents the progression of diet-induced NASH in mice. Methods: For 8 wk, female C57BL/6J mice (6-8 wk old) were pair-fed a liquid Western-style diet [WSD, 25% of energy from fat, 50% wt:wt fructose, 0.16% wt:wt cholesterol] or control diet (C diet) to induce liver damage. From week 8 to 13, they were pair-fed the C diet or WSD alone or supplemented with l-Gln to provide 2.1 g/kg body weight (C diet + Gln or WSD + Gln). Energy intake was adjusted to the group with the lowest energy intake. Indexes of liver damage and inflammation, intestinal barrier function, and toll-like receptor 4 (Tlr4) signaling in the liver were determined. Results: The liver histology scores significantly increased from 8 to 13 wk (+31%) in WSD-fed mice and were significantly higher than in controls (P ≤ 0.05 for both time comparisons), whereas scores did not differ between C diet-fed and WSD + Gln-fed mice after 13 wk of feeding. The occludin protein concentrations in the small intestinal tissue were similarly reduced in both WSD-fed groups when compared with controls [WSD compared with C diet (-53%) and C diet + Gln (-42%), P ≤ 0.05; WSD + Gln compared with C diet + Gln (-34%), P ≤ 0.05] after 13 wk, whereas the expression of myeloid differentiation primary response gene 88 mRNA and concentration of inducible nitric oxide synthase and 4-hydroxynonenal protein adducts were significantly higher only in livers of WSD-fed mice (P ≤ 0.05 for the WSD group compared with all other groups; WSD + Gln group compared with the C diet groups: NS). Conclusion: Taken together, our data suggest that oral Gln supplementation protects mice from the progression of pre-existing, WSD-induced NASH.
Authors: Laura Bordoni; Rosita Gabbianelli; Donatella Fedeli; Dennis Fiorini; Ina Bergheim; Cheng Jun Jin; Lisa Marinelli; Antonio Di Stefano; Cinzia Nasuti Journal: PLoS One Date: 2019-10-10 Impact factor: 3.240
Authors: Mariapia Vairetti; Laura Giuseppina Di Pasqua; Marta Cagna; Plinio Richelmi; Andrea Ferrigno; Clarissa Berardo Journal: Antioxidants (Basel) Date: 2021-02-28
Authors: Annette Brandt; Anika Nier; Cheng Jun Jin; Anja Baumann; Finn Jung; Vicent Ribas; Carmen García-Ruiz; Jose C Fernández-Checa; Ina Bergheim Journal: Redox Biol Date: 2018-12-23 Impact factor: 11.799