Abstract
Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes, but effects of sex chromosomes on circulating lipids and atherosclerosis are unknown. Here, we use mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We assess atherosclerosis in multiple models and experimental paradigms that distinguish effects of sex chromosomes, and male or female gonads. Pro-atherogenic lipids and atherosclerosis are greater in XX than XY mice, indicating a primary effect of sex chromosomes. Small intestine expression of enzymes involved in lipid absorption and chylomicron assembly are greater in XX male and female mice with higher intestinal lipids. Together, our results show that an XX sex chromosome complement promotes the bioavailability of dietary fat to accelerate atherosclerosis.
Original language | English |
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Article number | 2631 |
Journal | Nature Communications |
Volume | 10 |
Issue number | 1 |
DOIs | |
State | Published - Dec 1 2019 |
Bibliographical note
Publisher Copyright:© 2019, The Author(s).
Funding
L.A.C. is partially supported by R01HL107326 from the National Institutes of Health Heart Lung and Blood Institute (HLBI), for research support cores from P20GM103527 and P30GM127211 from the National Institute of General Medical Sciences, and from the American Heart Association (18SFRB3390001). P.T. was supported through an MMPC from the NIH (U2C DK059630). A.M. was supported for equipment acquisition by NIH 1S100D021753, from NIH HLBI R01 HL120507. M.P. was supported by NIH K99ES028734. A.P.A. was supported by NIH R01 HD076125, R01 DK083561. K.R. was supported by NIH R01 DL083561 and P01 HL028481. We acknowledge the medical illustrations provided by Tom Dolan, MS, from the University of Kentucky College of Medicine, for illustrations within Fig. 5F.
Funders | Funder number |
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National Institutes of Health National Heart, Lung, and Blood Institute | |
National Institutes of Health (NIH) | 1S100D021753, R01 HD076125, DK049630, R01 DK083561, P01 HL028481, 0D021753, HL107326, K99ES028734, DK120342, R01 DL083561, HLBI R01 HL120507 |
National Institutes of Health (NIH) | |
National Institute of General Medical Sciences | P30GM127211, P20GM103527 |
National Institute of General Medical Sciences | |
National Institute of Diabetes and Digestive and Kidney Diseases | U2CDK059630 |
National Institute of Diabetes and Digestive and Kidney Diseases | |
American the American Heart Association | 18SFRB3390001 |
American the American Heart Association |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy