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Sargassum fusiforme Fucoidan Ameliorates Obesity-Associated Metabolic Dysfunction via a Tauroursodeoxycholic
Hai Lin1, Ya Zhang2, Huanjuan Yan3
1Department of Endocrinology, Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China.
Abstract:
The global rise in obesity necessitates new therapeutic strategies. This study, for the first time, elucidates a novel indirect mechanism for the metabolic benefits of Sargassum fusiforme fucoidan (SFF). We found that SFF administration to obese (ob/ob) mice, while showing no direct effect on adipocytes in vitro, led to a significant 6.3-fold increase in serum tauroursodeoxycholic acid (TUDCA). This SFF-induced TUDCA elevation was identified as the key mediator for improving systemic insulin resistance (IR) and white adipose tissue (WAT) inflammation. Mechanistic studies revealed that TUDCA directly counteracted palmitic acid-induced lipotoxicity in adipocytes by activating the G protein-coupled bile acid receptor 5 (TGR5) and its downstream cAMP-PKA signaling pathway. This activation suppressed NF-κB-driven inflammation and inhibited pro-inflammatory arachidonic acid/linoleic acid (AA/LA) catabolism. Crucially, the in vivo therapeutic effects of SFF were phenocopied by direct TUDCA administration. These findings reveal a novel fucoidan-TUDCA-TGR5 axis, identifying TGR5 signaling as a promising therapeutic target for obesity-related metabolic diseases.
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