title: Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs.
abstract: Previously, we found that enteric lactoferrin (eLF) could reduce the visceral fat accumulation known to associate strongly with metabolic syndrome symptoms and consequently with an increased risk of atherosclerosis. In this study, the atherosclerosis-preventive potential of LF was assessed in a high-fat and high-cholesterol diet (HFCD)-induced hypercholesterolemia and atherosclerosis model using Microminipig™. Eight-week orally administered eLF remarkably reduced the HFCD-induced serum total and low-density lipoprotein cholesterol levels but not high-density lipoprotein cholesterol levels. A histological analysis of 15 arteries revealed that eLF systemically inhibited the development of atherosclerotic lesions. Pathway analysis using identified genes that characterized eLF administration in liver revealed significant changes in the steroid biosynthesis pathway (ssc00100) and all affected genes in this pathway were upregulated, suggesting that cholesterol synthesis inhibited by HFCD was recovered by eLF. In summary, eLF could potentially prevent the hypercholesterolemia and atherosclerosis through protecting homeostasis from HFCD-induced dysfunction of cholesterol metabolism.
authors.affiliation: a Life Science Research Laboratories , Research and Development Headquarters, Lion Corporation , Odawara , Japan.|b "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo , Tokyo , Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Morishita
authors.affiliation: c Department of Pathology , Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: a Life Science Research Laboratories , Research and Development Headquarters, Lion Corporation , Odawara , Japan.|d Advanced Medical Research Center , Yokohama City University , Yokohama , Japan.
authors.forename: Tomoji
authors.initials: T
authors.lastname: Ono
authors.affiliation: e Joint Faculty of Veterinary Medicine, Veterinary Teaching Hospital , Kagoshima University , Kagoshima , Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Miura
authors.affiliation: a Life Science Research Laboratories , Research and Development Headquarters, Lion Corporation , Odawara , Japan.|f Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Murakoshi
authors.affiliation: a Life Science Research Laboratories , Research and Development Headquarters, Lion Corporation , Odawara , Japan.|g Research Organization of Science and Engineering , Ritsumeikan University , Kusatsu , Japan.
authors.forename: Keikichi
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: b "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo , Tokyo , Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kato
authors.affiliation: c Department of Pathology , Kagoshima University Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.affiliation: f Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Hoyoku
authors.initials: H
authors.lastname: Nishino
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001158:Arteries; D050197:Atherosclerosis / Q000178:diet therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D059305:Diet, High-Fat; D005786:Gene Expression Regulation; D063990:Gene Ontology; D006937:Hypercholesterolemia / Q000178:diet therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D013552:Swine; D013556:Swine, Miniature; D014280:Triglycerides / Q000097:blood
chemical_list: D002791:Cholesterol, Dietary; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D007781:Lactoferrin
keywords: DNA microarray; LDL cholesterol; atherosclerosis; lactoferrin; microminipig