2. Academic Validation
  3. Sargassum fusiforme Fucoidan Ameliorates Obesity-Associated Metabolic Dysfunction via a Tauroursodeoxycholic Acid-Mediated TGR5-cAMP-PKA Signaling Pathway

Sargassum fusiforme Fucoidan Ameliorates Obesity-Associated Metabolic Dysfunction via a Tauroursodeoxycholic Acid-Mediated TGR5-cAMP-PKA Signaling Pathway

  • J Agric Food Chem. 2025 Aug 13;73(32):20235-20253. doi: 10.1021/acs.jafc.5c06044.
Hai Lin 1,  Ya Zhang 2,  Huanjuan Yan 3,  Cheng Wang 4,  Zhengshun Wen 4 5,  Haibin Tong 3 6,  Xiaoyan Pan 7 8
Affiliations

Affiliations

  • 1 Department of Endocrinology, Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China.
  • 2 Hepatology Diagnosis and Treatment Center & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 3 Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China.
  • 4 Xianghu Laboratory, Hangzhou 311231, China.
  • 5 Hangzhou Nutrition Biotechnology Co. Ltd., Hangzhou 311234, China.
  • 6 State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs,Beijing 100700, China.
  • 7 Department of Endocrinology and Metabolic Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 8 Wenzhou Key Laboratory of Diabetes Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
PMID: 40758868 DOI: 10.1021/acs.jafc.5c06044
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.

Keywords

TGR5; adipose tissue inflammation; fucoidan; insulin resistance; obesity; tauroursodeoxycholic acid.

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