Animal protein hydrolysate reduces visceral fat and inhibits insulin resistance and hepatic steatosis in aged mice

An increasing life expectancy in society has burdened healthcare systems substantially because of the rising prevalence of age-related metabolic diseases. This study compared the effects of animal protein hydrolysate (APH) and casein on metabolic diseases using aged mice. Eight-week-old and 50-week-old C57BL/6J mice were used as the non-aged (YC group) and aged controls (NC group), respectively. The aged mice were divided randomly into 3 groups (NC, low-APH [LP], and high-APH [HP] and fed each experimental diet for 12 weeks. In the LP and HP groups, casein in the AIN-93G diet was substituted with 16 kcal% and 24 kcal% APH, respectively. The mice were sacrificed when they were 63-week-old, and plasma and hepatic lipid, white adipose tissue weight, hepatic glucose, lipid, and antioxidant enzyme activities, immunohistochemistry staining, and mRNA expression related to the glucose metabolism on liver and muscle were analyzed. Supplementation of APH in aging mice resulted in a significant decrease in visceral fat (epididymal, perirenal, retroperitoneal, and mesenteric fat) compared to the negative control (NC) group. The intraperitoneal glucose tolerance test and area under the curve analysis revealed insulin resistance in the NC group, which was alleviated by APH supplementation. APH supplementation reduced hepatic gluconeogenesis and increased glucose utilization in the liver and muscle. Furthermore, APH supplementation improved hepatic steatosis by reducing the hepatic fatty acid and phosphatidate phosphatase activity while increasing the hepatic carnitine palmitoyltransferase activity. Furthermore, in the APH supplementation groups, the red blood cell (RBC) thiobarbituric acid reactive substances and hepatic H O levels decreased, and the RBC glutathione, hepatic catalase, and glutathione peroxidase activities increased. APH supplementation reduced visceral fat accumulation and alleviated obesity-related metabolic diseases, including insulin resistance and hepatic steatosis, in aged mice. Therefore, high-quality animal protein APH that reduces the molecular weight and enhances the protein digestibility-corrected amino acid score has potential as a dietary supplement for healthy aging.