Fan Gong; Yanru Ren; Tingting Cao; Yu Xu; Kun Wang; Jiarui Li; Ze Jin; Anle Wang; Jianning Li; Yi Yang & Yanhong Wei

Abnormal or excessive fat accumulation caused by a sedentary lifestyle and a high-fat diet (HFD) can lead to a loss of muscle mass and strength, ultimately resulting in sarcopenia, a condition known as sarcopenic obesity (SO). This study aimed to investigate the effects of Lycium barbarum polysaccharide (LBP) on SO and to explore the underlying mechanisms in order to evaluate its potential as a natural therapeutic agent. Male C57BL/6J mice were fed an HFD for 17 weeks, with LBP administration beginning after 8 weeks and continuing for 9 weeks. Body weight was measured twice weekly. Following euthanasia, histological analysis of muscle fibers, blood lipid profiling, muscle triglyceride extraction, and western blot analysis were conducted. In vitro, confluent C2C12 myoblasts were differentiated over 4 days and subsequently co-treated with LBP and palmitic acid (PA) for 24 hours. Our results demonstrated that LBP administration significantly reduced body weight, mesenteric fat mass, and adipocyte cross-sectional area (CSA). Concurrently, LBP increased muscle weight and muscle fiber CSA while decreasing the expression of atrophy-related markers, including muscle atrophy F-box protein (Atrogin-1) and muscle RING-finger protein 1 (MuRF1). Furthermore, LBP improved glucose tolerance and insulin sensitivity by modulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which also mitigated excessive lipid accumulation and ectopic fat deposition in skeletal muscle.Activation of the PI3K/AKT pathway by LBP enhanced muscle protein synthesis through increased phosphorylation of p70 ribosomal protein S6 kinase and inhibition of glycogen synthase kinase 3β, while simultaneously suppressing muscle protein degradation by downregulating the expression of Atrogin-1, MuRF1, myostatin, activin A receptor type II B (ActRIIB), and Smad2/3. These findings suggest that LBP is a promising natural agent for the prevention and treatment of SO, exerting its protective effects by correcting glucolipid metabolic disorders and restoring the balance between protein synthesis and degradation in skeletal muscle via the reactivation of the impaired PI3K/AKT pathway.

KEY WORDS: High-fat diet; Sarcopenic obesity; Lycium barbarum polysaccharide; PI3K/AKT pathway; Glucolipid metabolism.