Abstract: Objective The purpose of this study was to explore the intervening effect of L-ornithine L-aspartate (LOLA) on in mice with nonalcoholic steatohepatitis (NASH) and sarcopenic obesity. Methods 28 male C57BL/6 mice were randomly divided into control (n=11) and model group (n=17) and were fed with chow diet or high-fat diet, respectively. Five mice from each group were sacrificed to evaluate the establishment of NASH model after 12 weeks. The remaining mice fed with high fat diet were further randomized into the model control (n=6) and the intervention group (n=6) and were orally administrated with saline or LOLA solution once daily for 8 weeks. The pathological changes of liver and muscle were examined after execution. Results High-fat diet feeding for 12 weeks successfully established a NASH rodent model that presented with moderate-to-severe hepatic steatosis, lobular inflammatory cell infiltration, and hepatocyte ballooning; at the end of week 12, the grip strength of mice in model group was (100.2±1.8)g, significantly lower than in the control group; at the end of 20th week, the body fat mass and fat to body weight ratio of mice in the model control group were (8±0.7)g and (21.0±6.7)%, significantly higher than in the control group; the histopathological inflammatory severity of liver and muscle in the intervention group had significantly alleviated as compared to those in the model control group; the body fat mass and fat to body weight ratio in the intervention group were (3.7±0.3)g and (11.3±4.2)%, significantly lower than in the model control group (P<0.05); the lean body mass and grip strength in the intervention group were (75.2±2.7)% and (104.7±9.1)g, significantly higher than (64.7±3.2)% and (93.7±4.1)g in the model control group (P＜0.05); in the intervention group, the muscle cells were normal with the diameter of muscle fibers increased, and the NAS score in liver tissues decreased, relieved NASH obtained in all mice. Conclusion s Twenty-week high-fat diet could establish a mouse model that simultaneously exhibits steatohepatitis and sarcopenic obesity, and the application of LOLA exerts some degree of protection to these two injuries.

Key words: Nonalcoholic steatohepatitis, Sarcopenic obesity, L-ornithine L-aspartate, Mice