title: Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-A(y) mice.
abstract: 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.
authors.affiliation: Faculty of Fisheries Sciences, Hokkaido University, 3-1-1 Minato Hakodate, Hokkaido 041-8611, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Beppu
authors.forename: Masashi
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Niwano
authors.forename: Kazuo
authors.initials: K
authors.lastname: Miyashita
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D009929:Organ Size; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D024341:Xanthophylls / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D019440:Anti-Obesity Agents; D024341:Xanthophylls; C025164:fucoxanthin; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases