title: Effect of dietary n-3 fatty acids supplementation on fatty acid metabolism in atorvastatin-administered SHR.Cg-Leprcp/NDmcr rats, a metabolic syndrome model.
abstract: The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Leprcp/NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver.
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Mamun
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan. Electronic address: michio1@med.shimane-u.ac.jp.
authors.forename: Michio
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Katakura
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanabe
authors.affiliation: Disease Model Cooperative Research Association, Hamamatsu, Shizuoka, 433-8114, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Tsuchikura
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan; Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka-1342, Bangladesh.
authors.forename: Shahdat
authors.initials: S
authors.lastname: Hossain
authors.affiliation: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Shido
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018565:Food-Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D006937:Hypercholesterolemia / Q000188:drug therapy; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000924:Anticholesteremic Agents; D004041:Dietary Fats; D004338:Drug Combinations; C587319:TAK-085; D004281:Docosahexaenoic Acids; D000069059:Atorvastatin; D015118:Eicosapentaenoic Acid
keywords: Atorvastatin; Hypercholesterolemia and hyperlipidemia; Metabolic syndrome; N-3 PUFA