A novel rat model of sarcopenia based on lipopolysaccharide and high-fat diet

Objective Lipopolysaccharide (LPS) and a high-fat diet (HFD) over a long period of time can induce skeletal muscle atrophy, but their combined effects is unclear. Thus, the purpose of this study was to present a novel animal model of sarcopenia induced by LPS and HFD in male Sprague-Dawley (SD) rats and to compare the aging among the groups. Methods We divided 10-month-old male Sprague–Dawley (SD) rats into adult control (AC), low dose lipopolysaccharide (150 µg/kg)-high-fat diet group (LD-LPS-HFD), and high dose lipopolysaccharide (200 µg/kg)-high-fat diet group (HD-LPS-HFD). AC group rats were intraperitoneally injected with 0.9% physiological saline solution twice weekly and fed ordinary feed; while the two LPS-HFD groups were intraperitoneally injected with LPS twice a week and had a high-fat diet for 8 weeks. Sarcopenia index (SI), relative grip strength, hematoxylin & eosin staining, Sirius red staining, western blotting, and enzyme-linked immunosorbent assay verified sarcopenia. Results SI values in LD-LPS-HFD and HD-LPS-HFD were significantly decreased and the differences were more than twice the standard deviation of the AC group, indicating that sarcopenia model was successful. Although relative grip strength of rats in LD-LPS-HFD and HD-LPS-HFD were significantly reduced, only the difference in HD-LPS-HFD group was more than twice the standard deviation of the AC group, which was consistent with the characteristics of muscle strength decline in sarcopenia. Cross-sectional areas and fiber diameters of LD-LPS-HFD and HD-LPS-HFD decreased, but were lower in HD-LPS-HFD. Fibrosis, MuRF1, FbX32, and p53 protein expression in LD-LPS-HFD and HD-LPS-HFD were increased, but were higer in HD-LPS-HFD. p21, IL-6, and TNF-α level were significantly increased in HD-LPS-HFD. Conclusion Sarcopenia is induced by peritoneal injection of LPS (200 µg/kg) and a high-fat diet for 8 weeks in 10-month SD male rats. This model is suitable to study the prevention and treatment of sarcopenia and its molecular mechanisms.