β-胡萝卜素加氧酶 1 活性调节小鼠和人类循环胆固醇浓度。
β-Carotene Oxygenase 1 Activity Modulates Circulating Cholesterol Concentrations in Mice and Humans.
机构信息
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
出版信息
J Nutr. 2020 Aug 1;150(8):2023-2030. doi: 10.1093/jn/nxaa143.
BACKGROUND
Plasma cholesterol is one of the strongest risk factors associated with the development of atherosclerotic cardiovascular disease (ASCVD) and myocardial infarction. Human studies suggest that elevated plasma β-carotene is associated with reductions in circulating cholesterol and the risk of myocardial infarction. The molecular mechanisms underlying these observations are unknown.
OBJECTIVE
The objective of this study was to determine the impact of dietary β-carotene and the activity of β-carotene oxygenase 1 (BCO1), which is the enzyme responsible for the conversion of β-carotene to vitamin A, on circulating cholesterol concentration.
METHODS
In our preclinical study, we compared the effects of a 10-d intervention with a diet containing 50 mg/kg of β-carotene on plasma cholesterol in 5-wk-old male and female C57 Black 6 wild-type and congenic BCO1-deficient mice. In our clinical study, we aimed to determine whether 5 common small nucleotide polymorphisms located in the BCO1 locus affected serum cholesterol concentrations in a population of young Mexican adults from the Universities of San Luis Potosí and Illinois: A Multidisciplinary Investigation on Genetics, Obesity, and Social-Environment (UP AMIGOS) cohort.
RESULTS
Upon β-carotene feeding, Bco1-/- mice accumulated >20-fold greater plasma β-carotene and had ∼30 mg/dL increased circulating total cholesterol (P < 0.01) and non-HDL cholesterol (P < 0.01) than wild-type congenic mice. Our results in the UP AMIGOS cohort show that the rs6564851 allele of BCO1, which has been linked to BCO1 enzymatic activity, was associated with a reduction in 10 mg/dL total cholesterol concentrations (P = 0.009) when adjusted for vitamin A and carotenoid intakes. Non-HDL-cholesterol concentration was also reduced by 10 mg/dL when the data were adjusted for vitamin A and total carotenoid intakes (P = 0.002), or vitamin A and β-carotene intakes (P = 0.002).
CONCLUSIONS
Overall, our results in mice and young adults show that BCO1 activity impacts circulating cholesterol concentration, linking vitamin A formation with the risk of developing ASCVD.
背景
血浆胆固醇是与动脉粥样硬化性心血管疾病（ASCVD）和心肌梗死发展相关的最强危险因素之一。人体研究表明，升高的血浆β-胡萝卜素与循环胆固醇降低和心肌梗死风险降低有关。这些观察结果的分子机制尚不清楚。
目的
本研究旨在确定膳食β-胡萝卜素和β-胡萝卜素加氧酶 1（BCO1）的活性对循环胆固醇浓度的影响，BCO1 是负责将β-胡萝卜素转化为维生素 A 的酶。
方法
在我们的临床前研究中，我们比较了含有 50mg/kgβ-胡萝卜素的饮食干预对 5 周龄雄性和雌性 C57 黑 6 野生型和同源 BCO1 缺陷型小鼠血浆胆固醇的影响。在我们的临床研究中，我们旨在确定位于 BCO1 基因座的 5 个常见的小核苷酸多态性是否会影响来自圣路易斯波托西大学和伊利诺伊大学的年轻墨西哥成年人的血清胆固醇浓度：圣路易斯波托西大学和伊利诺伊大学的多学科遗传学、肥胖和社会环境研究（UP AMIGOS）队列。
结果
在用β-胡萝卜素喂养后，Bco1-/- 小鼠的血浆β-胡萝卜素积累量增加了 20 多倍，并且循环总胆固醇（P<0.01）和非高密度脂蛋白胆固醇（P<0.01）增加了约 30mg/dL，与野生型同源小鼠相比。我们在 UP AMIGOS 队列中的结果表明，与 BCO1 酶活性相关的 BCO1 基因座的 rs6564851 等位基因与总胆固醇浓度降低 10mg/dL 相关（调整维生素 A 和类胡萝卜素摄入量后，P=0.009）。当数据调整为维生素 A 和总类胡萝卜素摄入量（P=0.002）或维生素 A 和β-胡萝卜素摄入量（P=0.002）时，非高密度脂蛋白胆固醇浓度也降低了 10mg/dL。
结论
总体而言，我们在小鼠和年轻人中的研究结果表明，BCO1 活性会影响循环胆固醇浓度，将维生素 A 形成与 ASCVD 发病风险联系起来。
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