Fucoidan P Alleviates Sarcopenic Obesity by Regulating Muscle Protein and Energy Metabolism

Sarcopenic obesity (SO) is a complex condition involving increased fat accumulation along with reduced muscle mass and impaired muscle function; however, there are currently no approved pharmacological interventions targeting these pathological features.Akt and AMPK are key signaling pathways regulating muscle homeostasis and energy metabolism.Natural compounds that modulate these pathways may offer a promising multi-targeted therapeutic strategy.This study investigated the effects of Fucoidan P on SO and its underlying molecular pathways, while assessing translational relevance using clinical datasets.Fucoidan P decreased body weight and fat mass and size while improving grip strength, muscle mass, and fiber size during high-fat diet feeding.Fucoidan P mitigated muscle atrophy through phosphorylation of Akt, mTOR, and FOXO3a, and enhanced energy metabolism by activating the AMPK/SIRT1/PGC-1 pathway.Moreover, Fucoidan P downregulated PDE5A and PTGS1, which are identified differentially expressed genes-related to inflammation of clinical datasets, and inhibited pro-inflammatory cytokines by suppressing NF-B pathway.Taken together, these findings demonstrate that Fucoidan P alleviates SO by coordinately regulating muscle protein homeostasis, energy metabolism, and inflammatory responses through a network of interconnected Akt and AMPK/PGC-1, and NF-B signaling pathways, suggesting its potential as a multi-target therapeutic agent for SO.