The green algal carotenoid siphonaxanthin inhibits adipogenesis in 3T3-L1 preadipocytes and the accumulation of lipids in white adipose tissue of KK-Ay mice.
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.


CONCLUSIONS
These results provide evidence that siphonaxanthin may effectively regulate adipogenesis in 3T3-L1 cells and diabetic KK-Ay mice.
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan; and.
Zhuo-Si
ZS
Li
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan; and.
Kenji
K
Noda
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan; and.
Eriko
E
Fujita
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan; and.
Yuki
Y
Manabe
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan; and Department of Rehabilitation, Shijonawate Gakuen University, Osaka, Japan.
Takashi
T
Hirata
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan; and sugawara@kais.kyoto-u.ac.jp.
Tatsuya
T
Sugawara
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D000460:Chlorophyta / Q000737:chemistry*; D002784:Cholesterol / Q000097:blood; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D024341:Xanthophylls / Q000494:pharmacology*
D001786:Blood Glucose; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D014280:Triglycerides; D024341:Xanthophylls; C003314:siphonaxanthin; D002784:Cholesterol; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase
3T3-L1 cells; KK-Ay mice; adipogenesis; adipose tissue; marine carotenoids; siphonaxanthin