Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-Ay mice

Lipids in Health and Disease

Kazuo Miyashita¹  Yoshimi Niwano²  Masashi Hosokawa¹  Fumiaki Beppu¹ 

[1] Faculty of Fisheries Sciences, Hokkaido University, 3-1-1 Minato Hakodate, Hokkaido, 041-8611, Japan;Laboratory for Redox Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan

关键词: Proprotein convertase subtilisin/kexin type 9 (PCSK9);    Scavenger receptor class B type 1 (SR-B1);    Low-density lipoprotein (LDL) receptor (LDLR);    Sterol regulatory element binding protein (SREBP);    Liver;    Cholesterol metabolism;    Fucoxanthin;   

Others  :  1160214
DOI  :  10.1186/1476-511X-11-112

 received in 2012-08-01, accepted in 2012-09-03,  发布年份 2012

【 摘 要 】

Background

Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin.

Methods

Diabetic/obese KK-A^y mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively.

Results

Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), which enhances intracellular degradation of LDLR in lysosomes.

Conclusions

Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-A^y mice by inducing SREBP expression and reduced cholesterol uptake in the liver via down-regulation of LDLR and SR-B1, resulted in increased serum cholesterol in the mice.

【 授权许可】

   
2012 Beppu et al.; licensee BioMed Central Ltd.

【 图 表 】

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