Glycine protects against high sucrose and high fat-induced non-alcoholic steatohepatitis in rats

// Xin Zhou 1 , Dewu Han 1 , Ruiling Xu 1 , Huiwen Wu 1,2 , Chongxiao Qu 3 , Feng Wang 1 , Xiangyu Wang 4 and Yuanchang Zhao 1 1 Department of Pathophysiology, Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, China 2 Science & technology center of Fenyang College, Shanxi Medical University, Fenyang, Shanxi, China 3 Department of Pathology, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, China 4 Department of Oral Medicine, Shanxi Medical University, Taiyuan, Shanxi, China Correspondence to: Dewu Han, email: // Keywords : glycine, non-alcoholic steatohepatitis, intestinal endotoxin, endoplasmic reticulum stress, oxidative stress, Pathology Section Received : July 14, 2016 Accepted : October 12, 2016 Published : October 23, 2016 Abstract We set out to explore the hypothesis that glycine attenuates non-alcoholic steatohepatitis (NASH) in rats and the possible mechanism by which is it does. Male Sprague-Dawley (SD) rats were fed a diet containing high fat and high sucrose (HSHF) for 24 weeks to induce NASH. Blood and liver tissues were sampled at selected time points throughout the study. Compared with control animals, the content of alanine transaminase (ALT), triglycerides (TGs), and free fatty acids (FFAs) in plasma and the TG and FFA content in the liver was increased from week 4 to 24. The level of TNF α and MCP-1 in plasma, the content of TNF α in the liver, the insulin resistance index, inflammatory cell infiltration, hepatocyte apoptosis, reactive oxygen species (ROS) generation, and endoplasmic stress-associated protein expression were unaltered at 4 weeks. However, these levels were significantly elevated in HSHF fed rats at 12 weeks. At the same time, the level of endotoxin progressively increased from 0.08 ± 0.02 endotoxin EU/ml at week 4 to 0.7 ± 0.19 EU/ml at week 24. Moreover, these rats had elevated blood endotoxin levels, which were positively associated with their NASH indexes. Liver histology progressively worsened over the course of the study. However, we found that with concomitant treatment with glycine, the level of endotoxin decreased, while NASH indexes significantly decreased and liver status markedly improved,. These data support the hypothesis that glycine protects against NASH in rats by decreasing the levels of intestinal endotoxin, alleviating endoplasmic reticulum and oxidative stress.