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

Lipids in Health and Disease

Research

Kazuo Miyashita¹  Masashi Hosokawa¹  Fumiaki Beppu¹  Yoshimi Niwano² 

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

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

DOI  :  10.1186/1476-511X-11-112

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

来源: Springer

【 摘 要 】

BackgroundFucoxanthin 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.MethodsDiabetic/obese KK-Ay 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.ResultsDietary 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.ConclusionsFucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-Ay 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】

Unknown   
© Beppu et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.