title: Dietary alpha-cyclodextrin lowers low-density lipoprotein cholesterol and alters plasma fatty acid profile in low-density lipoprotein receptor knockout mice on a high-fat diet.
abstract: High dietary intake of saturated fat and cholesterol, and elevated low-density lipoprotein cholesterol levels are some of the modifiable risk factors for cardiovascular disease. Alpha-cyclodextrin (a-CD) when given orally has been shown in rats to increase fecal saturated fat excretion and to reduce blood total cholesterol levels in obese hypertriglyceridemic subjects with type 2 diabetes mellitus. In this study, the effects of dietary a-CD on lipid metabolism in low-density lipoprotein receptor knockout mice were investigated. Low-density lipoprotein receptor knockout mice were fed a "Western diet" (21% milk fat) with or without 2.1% of a-CD (10% of dietary fat content) for 14 weeks. At sacrifice, there was no difference in body weight; but significant decreases were observed in plasma cholesterol (15.3%), free cholesterol (20%), cholesterol esters (14%), and phospholipid (17.5%) levels in mice treated with alpha-CD compared with control mice. The decrease in total cholesterol was primarily in the proatherogenic apolipoprotein B-containing lipoprotein fractions, with no significant change in the high-density lipoprotein fraction. Furthermore, alpha-CD improved the blood fatty acid profile, reducing the saturated fatty acids (4.5%) and trans-isomers (11%) while increasing (2.5%) unsaturated fatty acids. In summary, the addition of alpha-CD improved the lipid profile by lowering proatherogenic lipoproteins and trans-fatty acids and by decreasing the ratio of saturated and trans-fatty acids to polyunsaturated fatty acids (-5.8%), thus suggesting that it may be useful as a dietary supplement for reducing cardiovascular disease.
authors.affiliation: Lipid Metabolism Section, NHLBI, NIH, Bethesda, MD 20892, USA.
authors.forename: Elke Maria
authors.initials: EM
authors.lastname: Wagner
authors.forename: Kai-Lin Catherine
authors.initials: KL
authors.lastname: Jen
authors.forename: Joseph Donald
authors.initials: JD
authors.lastname: Artiss
authors.forename: Alan Thomas
authors.initials: AT
authors.lastname: Remaley
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000378:metabolism* / Q000517:prevention & control; D001835:Body Weight / Q000187:drug effects; D002788:Cholesterol Esters / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage*; D004435:Eating / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D047391:alpha-Cyclodextrins / Q000494:pharmacology*
chemical_list: D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D011973:Receptors, LDL; D014280:Triglycerides; D047391:alpha-Cyclodextrins; C032613:alpha-cyclodextrin