Sellmann Cathrin, Baumann Anja, Brandt Annette, Jin Cheng Jun, Nier Anika, Bergheim Ina
Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany; and.
Molecular Nutritional Science Division, Department of Nutritional Sciences, University of Vienna, Vienna, Austria.
J Nutr. 2017 Nov;147(11):2041-2049. doi: 10.3945/jn.117.253815. Epub 2017 Sep 20.
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. The aim of the present study was to determine whether Gln prevents the progression of diet-induced NASH in mice. 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 () signaling in the liver were determined. The liver histology scores significantly increased from 8 to 13 wk (+31%) in WSD-fed mice and were significantly higher than in controls ( ≤ 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%), ≤ 0.05; WSD + Gln compared with C diet + Gln (-34%), ≤ 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 ( ≤ 0.05 for the WSD group compared with all other groups; WSD + Gln group compared with the C diet groups: NS). Taken together, our data suggest that oral Gln supplementation protects mice from the progression of pre-existing, WSD-induced NASH.
目前仍缺乏普遍接受的非酒精性脂肪性肝炎（NASH）治疗策略。研究表明，口服补充谷氨酰胺（Gln）对NASH的发展具有预防作用；然而，Gln对已存在的NASH是否也具有治疗潜力尚未明确。本研究的目的是确定Gln是否能预防饮食诱导的小鼠NASH进展。8周内，对雌性C57BL/6J小鼠（6 - 8周龄）进行配对喂养，给予液体西式饮食[WSD，25%的能量来自脂肪，50%重量比的果糖，0.16%重量比的胆固醇]或对照饮食（C饮食）以诱导肝损伤。从第8周到第13周，将它们单独配对喂养C饮食或WSD，或补充l - Gln以提供2.1 g/kg体重（C饮食 + Gln或WSD + Gln）。能量摄入量根据能量摄入量最低的组进行调整。测定肝损伤和炎症指标、肠道屏障功能以及肝脏中的Toll样受体4（TLR4）信号传导。在WSD喂养的小鼠中，肝脏组织学评分从8周增加到13周时显著升高（+31%），且显著高于对照组（两次时间比较均P≤0.05），而在喂养13周后，C饮食喂养组和WSD + Gln喂养组之间的评分没有差异。与对照组相比，在13周后，两个WSD喂养组的小肠组织中闭合蛋白浓度同样降低[WSD与C饮食相比（-53%）和C饮食 + Gln相比（-42%），P≤0.05；WSD + Gln与C饮食 + Gln相比（-34%），P≤0.05]，而仅在WSD喂养小鼠的肝脏中，髓样分化初级反应基因88 mRNA的表达、诱导型一氧化氮合酶的浓度和4 - 羟基壬烯醛蛋白加合物显著更高（WSD组与所有其他组相比P≤0.05；WSD + Gln组与C饮食组相比：无显著性差异）。综上所述，我们的数据表明，口服补充Gln可保护小鼠免受已存在的、WSD诱导的NASH进展的影响。
