Bovine Milk Fat Globule Epidermal Growth Factor VIII activates PI3K/Akt signaling pathway and attenuates sarcopenia in rat model induced by d-galactose

Abstract

To develop a more effective and safer treatment for sarcopenia, this research investigated the anti-sarcopenia mechanism of Milk Fat Globule Epidermal Growth Factor Ⅷ (MFG-E8) from the liver function and metabolism in sarcopenic model rat. After 4 weeks nutritional intervention experiment, MFG-E8 can significantly increase the gastrocnemius mass in rat. The mechanism of MFG-E8 in improving sarcopenia was related to its promotional capacity to the activities of superoxide dismutase (SOD) activity in serum, Glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) in liver. Meanwhile, MFG-E8 could also down-regulate obesity-related indicators, such as triglyceride (TG) and Non-esterified fatty acid (NEFA). The analysis of liver and gastrocnemius histopathology found that MFG-E8 could reduce the accumulation of fatty vesicles, improve liver function, thereby alleviating gastrocnemius tissue inflammation. In vitro experiments, myoblasts obtained from gastrocnemius tissue showed that MFG-E8 could reduce mitochondrial autophagy and inhibit cell apoptosis. In addition, MFG-E8 could up-regulate the phosphorylation level of PI3K via activating PI3K/Akt signaling pathway in gastrocnemius tissue, and promote the formation of muscle fibers, thereby increasing muscle mass. Moreover, MFG-E8 could also promote the formation of neuromuscular junctions by up-regulating the mRNA and protein expression of MusK in gastrocnemius.