Jaume Amengual1,2, Johana Coronel1, Courtney Marques2, Celia Aradillas-García3, Juan Manuel Vargas Morales4, Flavia C D Andrade5, John W Erdman1,2, Margarita Teran-Garcia2,6,7. 1. Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, USA. 2. Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA. 3. Facultad de Medicina/Coordination for the Innovation and Application of Science and Technology, CIACYT, Autonomous University of San Luis Potosí (UASLP), San Luis Potosí, Mexico. 4. Facultad de Ciencias Químicas, UASLP, San Luis Potosí, Mexico. 5. School of Social Work, University of Illinois at Urbana-Champaign, Urbana, IL, USA. 6. Department of Human Development and Family Studies, University of Illinois at Urbana-Champaign, Urbana, IL, USA. 7. Cooperative Extension, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Abstract
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.
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.
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