Lycium barbarum polysaccharide mitigates high-fat-diet-induced skeletal muscle atrophy by promoting AMPK/PINK1/Parkin-mediated mitophagy.

Sarcopenic obesity (SO) defined as the coexistence of obesity and sarcopenia. While the anti-obesity effects of Lycium barbarum polysaccharide (LBP), the main component of L. barbarum extract, are known, its efficacy against SO remains unexplored. Consequently, we aimed to investigate the therapeutic effects of LBP on SO and the elucidate the underlying mechanisms. Our results revealed that LBP administration decreased obesity-related factors, and increased muscle-related factors in mice fed a high-fat diet (HFD). LBP administration ameliorated PA- and HFD-induced hyperglycaemia by modulating IRS-1 and GLUT-4 levels while also mitigating the ectopic fat deposition. Furthermore, our results demonstrated that LBP can mitigate mitochondrial structural abnormalities and dysfunction-characterized by increased mitochondrial membrane potential and ATP levels, reduced reactive oxygen species levels-through the activation of mitophagy. However, these beneficial effects of LBP on skeletal muscle were negated by AMPK inhibitor and siRNA knockdown of Parkin expression. Taken together, our findings indicate that LBP may effectively modulate glucose and lipid metabolism while ameliorating skeletal muscle atrophy via the activation of the AMPK/PINK1/Parkin-mediated mitophagy pathway, thereby repairing the mitochondrial structure and function. Consequently, LBP emerges as a promising therapeutic candidate for addressing obesity-related impacts on skeletal muscle.