SHRSP5/Dmcr rats fed a high-fat and high-cholesterol diet develop disease-induced sarcopenia as nonalcoholic steatohepatitis progresses.

BACKGROUND:Secondary sarcopenia develops as a result of a bedridden state and illnesses, such as cachexia, liver disease, and diabetes. However, there is a lack of animal models to investigate the underlying mechanisms and potential treatments for secondary sarcopenia. Recently, secondary sarcopenia has been associated with the prognosis of nonalcoholic steatohepatitis. This study aimed to investigate whether stroke-prone spontaneously hypertensive rat 5 (SHRSP5/Dmcr) which developed severe nonalcoholic steatohepatitis by a high-fat and high-cholesterol (HFC; containing 2% cholic acid) diet is a useful model of secondary sarcopenia. METHODS:SHRSP5/Dmcr rats were divided into 6 groups fed with a Stroke-Prone (SP: normal chow) or HFC diets for different periods (4, 12, and 20 weeks), and WKY/Izm rats were divided into 2 groups fed an SP or HFC diet. Body weight, food intake, and muscle force were measured weekly for all rats. After the end of the diet period, skeletal muscle strength evoked by electrical stimulation was recorded, blood was collected, and organ weight was measured. The sera were used for biochemical analysis and the organs were used for histopathological analysis. RESULTS:SHRSP5/Dmcr rats fed an HFC diet developed nonalcoholic steatohepatitis, and their skeletal muscles, especially fast muscles, showed atrophy, indicating that muscle atrophy is aggravated by the progression of nonalcoholic steatohepatitis. In contrast, WKY/Izm rats fed an HFC diet did not exhibit sarcopenia. CONCLUSIONS:This study suggests that SHRSP5/Dmcr rats could be a useful novel model for investigate the mechanism of secondary sarcopenia disorder associated with nonalcoholic steatohepatitis.