Fucoidan improves serum lipid levels and atherosclerosis through hepatic SREBP-2-mediated regulation.
Hyperlipidemia is associated with increased risk of the development of cardiovascular diseases. Although a great deal of attention has been paid to the hypolipidemic activity of fucoidan, complex polysaccharides from brown seaweeds, the underlying mechanism is still unclear. This study was performed to investigate whether and how fucoidan has lipid-lowering potential in poloxamer-407 (P407)-induced hyperlipidemic mice. Fucoidan treatment 2 h after acute administration of P407 in these mice significantly reduced serum total cholesterol, triglycerides, and LDL cholesterol levels, but increased the levels of HDL cholesterol. In HepG2 hepatocytes and the liver, fucoidan decreased the expression of FAS and ACC mRNA with no or only a moderate inhibitory effect on SREBP-1c mRNA expression. Furthermore, fucoidan attenuated the hepatic expression of mature SREBP-2 protein with a subsequent decrease in hepatic HMG-CoA reductase mRNA expression and an increase in hepatic LDL receptor mRNA expression. In addition, atherosclerotic lesions in the aorta of chronically P407-treated mice were also reduced by fucoidan. These findings indicate that fucoidan improves serum lipid levels by regulating the expression of key enzymes of cholesterol and triglyceride syntheses in the liver through modulation of SREBP-2.
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Jinhee
J
Park
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Mijung
M
Yeom
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: dhhahm@khu.ac.kr.
Dae-Hyun
DH
Hahm
D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D020442:Poloxamer; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism*
D000960:Hypolipidemic Agents; D008055:Lipids; D011134:Polysaccharides; D051782:Sterol Regulatory Element Binding Protein 2; D020442:Poloxamer; C007789:fucoidan
Fucoidan; HepG2 cell; Hyperlipidemia; Poloxamer-407; Sterol regulatory element-binding protein-1c/2