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-1α 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-κB 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-1α, and NF-κB signaling pathways, suggesting its potential as a multi-target therapeutic agent for SO.