Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs

• Published in: Bioscience, biotechnology, and biochemistry Vol. 80; no. 2; pp. 295 - 303
• Main Authors: Morishita, Satoru, Kawaguchi, Hiroaki, Ono, Tomoji, Miura, Naoki, Murakoshi, Michiaki, Sugiyama, Keikichi, Kato, Hisanori, Tanimoto, Akihide, Nishino, Hoyoku
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.02.2016
• Subjects: Administration, Oral; Animals; Arteries; atherosclerosis; Atherosclerosis - diet therapy; Atherosclerosis - etiology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Cholesterol, Dietary - adverse effects; Diet, High-Fat; DNA microarray; Gene Expression Regulation; Gene Ontology; Hypercholesterolemia - diet therapy; Hypercholesterolemia - etiology; Hypercholesterolemia - metabolism; Hypercholesterolemia - pathology; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - metabolism; lactoferrin; Lactoferrin - pharmacology; LDL cholesterol; Lipoproteins, HDL - blood; Lipoproteins, LDL - blood; Liver - drug effects; Liver - metabolism; Male; microminipig; Molecular Sequence Annotation; Oligonucleotide Array Sequence Analysis; Signal Transduction; Swine; Swine, Miniature; Triglycerides - blood; DNA microarray; atherosclerosis; lactoferrin; LDL cholesterol; microminipig
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2015.1091713

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.