Lipopolysaccharide and high-fat diet–induced sarcopenia in rats: An exploratory study for sarcopenia model

Background: The occurrence of sarcopenia escalates swiftly as age advances. Both lipopolysaccharide (LPS) and a prolonged high-fat diet (HFD) can trigger skeletal muscle wasting, yet the combined impact of these 2 factors remains an enigma. Objective: To present an animal model of sarcopenia induced by LPS and HFD in rats. Methods: We divided 10-month-old male Sprague-Dawley (SD) rats into a control group, low-dose LPS (150 µg/kg)-HFD group (LD-LPS-HFD), and high-dose LPS (200 µg/kg)-HFD group (HD-LPS-HFD). Control group rats were intraperitoneally injected with 0.9% physiological saline solution and fed ordinary feed, while the 2 LPS-HFD groups were intraperitoneally injected with LPS twice a week and had a HFD for 8 weeks. Sarcopenia Index, relative grip strength, hematoxylin and eosin staining, Sirius red staining, western blotting, and enzyme-linked immunosorbent assay verified sarcopenia. Results: Sarcopenia Index values in LD-LPS-HFD and HD-LPS-HFD were significantly decreased, and the differences were more than twice the SD of the control group, indicating that the sarcopenia model was successful. Although the relative grip strength of rats in LD-LPS-HFD and HD-LPS-HFD were significantly reduced, only the difference in the HD-LPS-HFD group was more than twice the SD of the control 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 higher in HD-LPS-HFD. p21, interleukin 6, and tumor necrosis factor-alpha levels were significantly increased in HD-LPS-HFD. Conclusion: The study shows that a combined intervention of 200 µg/kg LPS injections and a HFD for 8 weeks in middle-aged rats effectively mimics sarcopenia, causing muscle mass and strength loss, cellular atrophy, interstitial fiber infiltration, increased inflammation, and higher aging marker expression.