β-Carotene Oxygenase 1 Activity Modulates Circulating Cholesterol Concentrations in Mice and Humans.
atherosclerosis
genetic variants
micronutrients
nutrition
retinoic acid
Journal
The Journal of nutrition
ISSN: 1541-6100
Titre abrégé: J Nutr
Pays: United States
ID NLM: 0404243
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
received:
12
12
2019
revised:
16
03
2020
accepted:
28
04
2020
pubmed:
21
5
2020
medline:
11
11
2020
entrez:
21
5
2020
Statut:
ppublish
Résumé
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. 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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 32433733
pii: S0022-3166(22)02270-2
doi: 10.1093/jn/nxaa143
pmc: PMC7398780
doi:
Substances chimiques
beta Carotene
01YAE03M7J
Cholesterol
97C5T2UQ7J
Dioxygenases
EC 1.13.11.-
Bco1 protein, mouse
EC 1.13.11.63
BCO2 protein, human
EC 1.14.99.-
beta-Carotene 15,15'-Monooxygenase
EC 1.14.99.36
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2023-2030Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL147252
Pays : United States
Informations de copyright
Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.
Références
Nutr Rev. 2019 Jan 1;77(1):32-45
pubmed: 30202882
Arterioscler Thromb Vasc Biol. 2015 Aug;35(8):1778-86
pubmed: 26112012
Nucleic Acids Res. 2003 Jul 1;31(13):3651-3
pubmed: 12824386
J Nutr. 2008 Oct;138(10):1923-30
pubmed: 18806102
Adv Healthc Mater. 2017 Oct;6(20):
pubmed: 28730752
J Nutr. 2014 Jul;144(7):1067-74
pubmed: 24744306
J Biol Chem. 2000 Apr 21;275(16):11915-20
pubmed: 10766819
Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2160-4
pubmed: 8384714
BMC Genomics. 2013 Aug 28;14:575
pubmed: 23981290
J Biol Chem. 2013 Nov 22;288(47):34081-34096
pubmed: 24106281
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10581-6
pubmed: 12136129
Circulation. 2019 Jun 18;139(25):e1082-e1143
pubmed: 30586774
Am J Hum Genet. 2009 Feb;84(2):123-33
pubmed: 19185284
Salud Publica Mex. 1998 Mar-Apr;40(2):133-40
pubmed: 9617194
FASEB J. 2009 Apr;23(4):1041-53
pubmed: 19103647
Nature. 2012 Nov 1;491(7422):56-65
pubmed: 23128226
J Nutr. 2016 Sep;146(9):1866S-73S
pubmed: 27511936
Biomed Res Int. 2015;2015:758723
pubmed: 25802864
Br J Nutr. 2015 Aug 28;114(4):509-18
pubmed: 26201974
Am J Cardiol. 2009 Aug 15;104(4):548-53
pubmed: 19660610
Bioinformatics. 2002 Feb;18(2):333-4
pubmed: 11847087
World Health Organ Tech Rep Ser. 1995;854:1-452
pubmed: 8594834
J Am Coll Cardiol. 2018 Oct 30;72(18):2181-2197
pubmed: 30360827
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Nov;1865(11):158580
pubmed: 31794861
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Nov;1865(11):158635
pubmed: 31978554
Hum Hered. 2013;75(2-4):152-9
pubmed: 24081231
J Biol Chem. 2013 Mar 29;288(13):9017-27
pubmed: 23393141
Clin Chem. 1972 Jun;18(6):499-502
pubmed: 4337382
PLoS One. 2015 Jan 28;10(1):e0115272
pubmed: 25629601
J Am Coll Cardiol. 2017 Dec 19;70(24):2979-2991
pubmed: 29241485
Methods Mol Biol. 2009;530:423-33
pubmed: 19266333
N Engl J Med. 2017 Sep 28;377(13):1284-1285
pubmed: 28953440
Hum Mol Genet. 2015 Jun 1;24(11):3206-19
pubmed: 25701869
Lifestyle Genom. 2018;11(1):40-48
pubmed: 29847832
Am J Epidemiol. 1985 Jul;122(1):51-65
pubmed: 4014201
J Biol Chem. 2007 Nov 16;282(46):33553-33561
pubmed: 17855355
ACS Chem Biol. 2018 Aug 17;13(8):2121-2129
pubmed: 29883100
Curr Opin Lipidol. 2019 Oct;30(5):401-408
pubmed: 31361625
PLoS One. 2011;6(6):e20644
pubmed: 21673813
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Circ Res. 2016 Aug 5;119(4):557-63
pubmed: 27323773
Arch Med Res. 1999 May-Jun;30(3):224-39
pubmed: 10427874
J Biol Chem. 2012 Jul 13;287(29):24216-27
pubmed: 22637576
J Biol Chem. 2010 Sep 3;285(36):27891-9
pubmed: 20573961
J Clin Invest. 1995 Oct;96(4):2075-82
pubmed: 7560102
J Biol Chem. 2008 Feb 22;283(8):4905-11
pubmed: 18093975
Nature. 2010 Aug 5;466(7307):714-9
pubmed: 20686566
Nutrients. 2019 Apr 13;11(4):
pubmed: 31013923
J Clin Endocrinol Metab. 2016 Apr;101(4):1686-92
pubmed: 26863424
J Nutr. 2012 Jan;142(1):161S-5S
pubmed: 22113863
J Clin Endocrinol Metab. 2017 Jun 1;102(6):1983-1990
pubmed: 28323947
Circ Res. 2018 Dec 7;123(12):1339-1349
pubmed: 30566060