title: Fucoidan alleviates high-fat diet-induced dyslipidemia and atherosclerosis in ApoE(shl) mice deficient in apolipoprotein E expression.
abstract: Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, possesses many biological activities including anti-inflammatory and antioxidant activities. We aimed to investigate the protective effects of fucoidan on dyslipidemia and atherosclerosis in apolipoprotein E-deficient mice (ApoE(shl) mice) and to elucidate its molecular targets in the liver by using a transcriptomic approach. For 12weeks, ApoE(shl) mice were fed a high-fat diet (HFD) supplemented with either 1% or 5% fucoidan. Fucoidan supplementation significantly reduced tissue weight (liver and white adipose tissue), blood lipid, total cholesterol (TC), triglyceride (TG), non-high-density lipoprotein cholesterol (non-HDL-C) and glucose levels in HFD-fed ApoE(shl) mice but increased plasma lipoprotein lipase (LPL) activity and HDL-C levels. Fucoidan also reduced hepatic steatosis levels (liver size, TC and TG levels, and lipid peroxidation) and increased white adipose tissue LPL activity. DNA microarray analysis and quantitative reverse transcription-polymerase chain reaction demonstrated differential expression of genes encoding proteins involved in lipid metabolism, energy homeostasis and insulin sensitivity, by activating Ppara and inactivating Srebf1. Fucoidan supplementation markedly reduced the thickness of the lipid-rich plaque, lipid peroxidation and foaming macrophage accumulation in the aorta in HFD-fed ApoE(shl) mice. Thus, fucoidan supplementation appears to have anti-dyslipidemic and anti-atherosclerotic effects by inducing LPL activity and inhibiting the effects of inflammation and oxidative stress in HFD-fed ApoE(shl) mice.
authors.affiliation: Department of Molecular Biology, Institute for Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki 1-396, Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan. Electronic address: taka@nms.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Department of Neurology, Shioda Hospital, Idemizu 1221, Katsuura-Shi, Chiba, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Division of Internal Medicine, Kaihin Park Clinic, 2-1-2-5 Utase, Mihama-ku, Chiba-city, Chiba, 261-0013, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Nagashima
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki 1-396, Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamimura
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D050171:Dyslipidemias / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015227:Lipid Peroxidation; D008071:Lipoprotein Lipase / Q000097:blood; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008815:Mice, Inbred Strains; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D009929:Organ Size; D018384:Oxidative Stress; D000459:Phaeophyceae / Q000737:chemistry; D011134:Polysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D012624:Seaweed / Q000737:chemistry; D017539:Tunica Intima / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D000960:Hypolipidemic Agents; D011134:Polysaccharides; C007789:fucoidan; D008071:Lipoprotein Lipase
keywords: ApoE(shl) mice; Atherosclerosis; Dyslipidemia; Fucoidan; High-fat diet