The Green Algal Carotenoid Siphonaxanthin Inhibits Adipogenesis in 3T3-L1 Preadipocytes and the Accumulation of Lipids in White Adipose Tissue of KK-Ay Mice1–3

Abstract

Background: Siphonaxanthin, a xanthophyll present in green algae, has been shown to possess antiangiogenic and apoptosis-inducing activities.Objective: We evaluated the antiobesity effects of siphonaxanthin by using a 3T3-L1 cell culture system and in diabetic KK-Ay mice.Methods: 3T3-L1 cells were differentiated with or without 5 μmol/L siphonaxanthin, and lipid accumulation and critical gene expressions for adipogenesis were examined. In vivo, 4-wk-old male KK-Ay mice were administered daily oral treatment of 1.3 mg siphonaxanthin for 6 wk and body weight, visceral fat weight, serum variables, and gene expressions involved in lipid metabolism were evaluated.Results: Compared with the other carotenoids evaluated, siphonaxanthin potently inhibited adipocyte differentiation. Siphonaxanthin significantly suppressed lipid accumulation at noncytotoxic concentrations of 2.5 and 5 μmol/L by 29% and 43%, respectively. The effects of siphonaxanthin were largely limited to the early stages of adipogenesis. Siphonaxanthin significantly inhibited protein kinase B phosphorylation by 48% and 72% at 90 and 120 min, respectively. The expressions of key adipogenesis genes, including CCAAT/enhancer binding protein α (Cebpa), peroxisome proliferator activated receptor γ (Pparg), fatty acid binding protein 4 (Fabp4), and stearoyl coenzyme A desaturase 1 (Scd1), were elevated by 1.6- to 166-fold during adipogenesis. After 8 d of adipocyte differentiation, siphonaxanthin significantly lowered gene expression of Cebpa, Pparg, Fabp4, and Scd1 by 94%, 83%, 95%, and 90%, respectively. Moreover, oral administration of siphonaxanthin to KK-Ay mice significantly reduced the total weight of white adipose tissue (WAT) by 13%, especially the mesenteric WAT by 28%. Furthermore, siphonaxanthin administration reduced lipogenesis and enhanced fatty acid oxidation in adipose tissue. Siphonaxanthin was observed to highly accumulate in mesenteric WAT, and the accumulation in the mesenteric WAT was almost 2- and 3-fold that in epididymal (P = 0.14) and perirenal (P < 0.05) WAT, respectively.Conclusion: These results provide evidence that siphonaxanthin may effectively regulate adipogenesis in 3T3-L1 cells and diabetic KK-Ay mice.