Oral Supplementation of Glutamine Attenuates the Progression of Nonalcoholic Steatohepatitis in C57BL/6J Mice. Issue 11 (20th September 2017)

• Record Type: Journal Article
• Authors: Sellmann, Cathrin; Baumann, Anja; Brandt, Annette; Jin, Cheng Jun; Nier, Anika; Bergheim, Ina
• Is Part Of: Journal of nutrition. Volume 147:Issue 11(2017)
• Page Start: 2041
• Page End: 2049
• Publication Date: 2017-09-20
• Subjects: hepatic inflammation -- insulin resistance -- lipid peroxidation -- liver damage -- neutrophils -- toll-like receptor 4 signaling -- Western-style diet; Nutrition -- Periodicals; Diet -- Periodicals; 613.205
• DOI: 10.3945/jn.117.253815
• Languages: English
• ISSNs: 0022-3166

Abstract

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.