Sarcopenia is a disease characterized by skeletal muscle mass loss. Sarcopenia was initially thought to be an age-related disease; however, sarcopenia induced by age is now defined as primary sarcopenia whereas sarcopenia caused by malnutrition and diseases, including cachexia, diabetes, chronic kidney disease, is defined as secondary sarcopenia (Liccini and Malmstrom, 2016, Meza-Valderrama et al., 2021, Sabatino et al., 2021). In addition to skeletal muscle mass loss, sarcopenia is characterized by a decrease in muscle strength and/or physical function (Chen et al., 2020, Cruz-Jentoft and Sayer, 2019). Moreover, the prognosis of sarcopenia is worse in patients with malnutrition and other diseases. As older adults are more likely to develop sarcopenia, early therapeutic diagnosis and intervention are key to the treatment of sarcopenia, especially in developed countries with aging populations. Treatments for sarcopenia include exercise and branched-chain amino acid replacement therapy; however, the therapeutic effects of these treatments are not clear (Hiraoka et al., 2017, Mohta et al., 2022). Therefore, basic research is needed to validate prevention and/or treatment methods for sarcopenia.

Nonalcoholic fatty liver disease (NAFLD) is a phenotype of metabolic syndrome. NAFLD is classified into 2 phenotypes: nonalcoholic fatty liver (NAFL), which is characterized by a fatty liver, and nonalcoholic steatohepatitis (NASH), which is characterized by steatosis and fibrosis. In recent years, approximately 25–45% of the world’s population has been affected by NAFLD, and 20% of patients with NAFL progress to NASH (Nd, 2019, Rinella, 2015). Moreover, some patients with NAFLD/NASH develop cirrhosis and hepatocellular carcinoma (Younossi et al., 2016). The relationship between NAFLD/NASH and sarcopenia has received significant attention in recent years; sarcopenia is associated with a poor prognosis in patients with NAFLD/NASH (Habig et al., 2021, Koo et al., 2017, Lee et al., 2015, Yu et al., 2018). Sarcopenia has been implicated in the pathogenesis of NAFLD/NASH independently of aging, obesity, and insulin resistance, and in lean NASH, which is particularly problematic in Asian countries (Koo et al., 2017, Younes and Bugianesi, 2019). In addition, protein-energy malnutrition and hyperammonemia were reported to be associated with sarcopenia and chronic liver diseases, including NAFLD/NASH. Although animal models of NAFLD/NASH with sarcopenia for basic research have been reported, these animals exhibited mild hepatic fibrosis whereas severe hepatic fibrosis has been observed as the pathological manifestation of sarcopenia in humans. Therefore, an optimal animal model of sarcopenia has not been established yet (Cabrera et al., 2016, Nachit et al., 2021).

Stroke-prone spontaneously hypertensive rat 5 (SHRPS5/Dmcr) is an animal that develops NASH with severe fibrosis when fed a high-fat and high-cholesterol (HFC) diet (Kitamori et al., 2012). In this study, we investigated the physiological, biochemical, and pathological changes in SHRSP5/Dmcr rats fed an HFC diet for 4, 12, and 20 weeks, and investigated its use as a new animal model for disease-induced sarcopenia.