title: Complementary Cholesterol-Lowering Response of a Phytosterol/α-Lipoic Acid Combination in Obese Zucker Rats.
abstract: To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (-55%) than either the PS (-24%) or the αLA (-25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (-47%) or in combination with PS (-54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21-22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone.
authors: a 1 Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions , University at Buffalo , Buffalo , NY , USA.
authors: Todd C
authors: TC
authors: Rideout
authors: a 1 Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions , University at Buffalo , Buffalo , NY , USA.
authors: Bradley
authors: B
authors: Carrier
authors: a 1 Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions , University at Buffalo , Buffalo , NY , USA.
authors: Shin
authors: S
authors: Wen
authors: a 1 Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions , University at Buffalo , Buffalo , NY , USA.
authors: Amy
authors: A
authors: Raslawsky
authors: b 2 Biotechnical and Clinical Laboratory Sciences, University at Buffalo , Buffalo, NY, USA.
authors: Richard W
authors: RW
authors: Browne
authors: c 3 Diabetes and Nutritional Sciences Division, Faculty of Life Sciences and Medicine, King's College London , London , United Kingdom.
authors: Scott V
authors: SV
authors: Harding
mesh_terms: D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D019587:Dietary Supplements; D004357:Drug Synergism; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000150:complications*; D010840:Phytosterols / Q000494:pharmacology* / Q000627:therapeutic use; D000071449:Proprotein Convertase 9; D012333:RNA, Messenger / Q000378:metabolism; D011924:Rats, Zucker; D012697:Serine Endopeptidases / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000214:Acyl Coenzyme A; D000924:Anticholesteremic Agents; D000975:Antioxidants; D001647:Bile Acids and Salts; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; D010840:Phytosterols; D012333:RNA, Messenger; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D008063:Thioctic Acid; D002784:Cholesterol; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9; D012697:Serine Endopeptidases
keywords: Alpha lipoic acid; high fat diet; lipids; lipoproteins; phytosterols