Rideout Todd C, Carrier Bradley, Wen Shin, Raslawsky Amy, Browne Richard W, Harding Scott V
a 1 Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions , University at Buffalo , Buffalo , NY , USA.
b 2 Biotechnical and Clinical Laboratory Sciences, University at Buffalo , Buffalo, NY, USA.
J Diet Suppl. 2016;13(3):283-99. doi: 10.3109/19390211.2015.1008616. Epub 2015 Feb 9.
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.
为研究植物甾醇/α-硫辛酸（PS/αLA）疗法降低胆固醇的效果，将32只雄性 Zucker 大鼠随机分为4组，每组采用一种饮食方案，持续30天：（i）高脂饮食（HF，40%的能量来自脂肪）；（ii）添加3%植物甾醇的HF饮食；（iii）添加0.25%α-硫辛酸的HF饮食；或（iv）添加3%PS和0.25%α-硫辛酸的HF饮食（PS/αLA）。与HF饮食相比，PS/αLA联合疗法在降低非HDL胆固醇方面（-55%）比单独使用PS（-24%）或α-硫辛酸（-25%）疗法更有效。补充PS不影响LDL颗粒数量，然而，单独补充α-硫辛酸（-47%）或与PS联合补充（-54%）时可减少LDL颗粒数量。与喂食HF的动物相比，所有治疗组中HDL颗粒数量增加的证据都在相似程度上明显（21%-22%）。PS介导的肠道胆固醇吸收中断表现为粪便胆固醇损失增加（+52%）和HMG-CoA还原酶mRNA代偿性增加（HF的1.6倍），然而，补充α-硫辛酸不影响粪便胆固醇损失。肝脏mRNA和蛋白质表达模式表明，α-硫辛酸调节胆固醇稳态的多个方面，包括合成减少（HMG-CoA还原酶mRNA，HF的0.7倍）、胆汁酸合成减少（CYP7a1表达，HF的0.17倍）以及胆固醇清除增加（PCSK9 mRNA减少，HF的0.5倍；LDLr蛋白增加，HF的2倍）。综上所述，这些数据表明，PS和α-硫辛酸通过独特且互补的机制发挥作用，比单独使用任何一种疗法都能提供更优且更全面的降胆固醇反应。
