Abstract: Sea cucumber fucoidan (SC-FUC) is one of the important bioactive components in the body wall of sea cucumber. Previous studies have shown that the biological activity of polysaccharides is closely related to their advanced structure. However, there are few reports on the association between the advanced structure of SC-FUC and its inhibitory activity against adipocyte differentiation. This work studied the effect of fucoidan from Holothuria mexicana (Hm-FUC) with different advanced structures on adipocyte differentiation, aiming to provide a theoretical basis for efficient utilization and development of SC-FUC. 3T3-L1 preadipocytes were differentiated into adipocytes by using the traditional cocktail method. The regulatory effect and molecular mechanism of Hm-FUC with different advanced structures on the differentiation of 3T3-L1 preadipocytes were studied by methyl thiazolyl tetrazolium assay, Oil Red O staining and reverse transcription real-time polymerase chain reaction. The results showed that all four Hm-FUCs tested significantly inhibited the proliferation and differentiation of 3T3-L1 preadipocytes, reduced the number of mature adipocytes, and decreased intracellular triglyceride levels. Moreover, they significantly downregulated the mRNA expression of crucial transcription factors regulating adipocyte differentiation such as SREBP1c, PPARγ, and C/EBPα (P < 0.05), upregulated the mRNA expression of key genes in the Wnt/β-catenin signaling pathway such as LRP5, LRP6, Frz, β-catenin, cmyc and Cyclin D1, and downregulated the mRNA expression of the negative regulatory factor GSK3β (P < 0.05), with Hm3 (210 kDa, with random coil short-chain configuration) showing the most significant effect. However, these Hm-FUCs showed no significant impact on the mRNA expression of Wnt10b. It is suggested that Hm-FUC could inhibit adipogenesis via activating the Wnt/β-catenin signaling pathway to downregulate the mRNA expression of the key transcription factors involved in adipocyte differentiation. Notably, the polysaccharide with molecular mass of 210 kDa and random coil short-chain configuration had the strongest inhibitory activity against adipocyte differentiation.

Key words: sea cucumber fucoidan; molecular mass; chain conformation; adipocyte differentiation; Wnt/β-catenin pathway