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Publication
Increased high-density lipoprotein cholesterol levels in mice with XX versus XY
sex chromosomes.
Authors Link JC, Chen X, Prien C, Borja MS, Hammerson B, Oda MN, Arnold AP, Reue K
Submitted By Submitted Externally on 10/1/2015
Status Published
Journal Arteriosclerosis, thrombosis, and vascular biology
Year 2015
Date Published 8/1/2015
Volume : Pages 35 : 1778 - 86
PubMed Reference 26112012
Abstract The molecular mechanisms underlying sex differences in dyslipidemia are poorly
understood. We aimed to distinguish genetic and hormonal regulators of sex
differences in plasma lipid levels., We assessed the role of gonadal hormones
and sex chromosome complement on lipid levels using the four core genotypes
mouse model (XX females, XX males, XY females, and XY males). In gonadally
intact mice fed a chow diet, lipid levels were influenced by both male-female
gonadal sex and XX-XY chromosome complement. Gonadectomy of adult mice revealed
that the male-female differences are dependent on acute effects of gonadal
hormones. In both intact and gonadectomized animals, XX mice had higher HDL
cholesterol (HDL-C) levels than XY mice, regardless of male-female sex. Feeding
a cholesterol-enriched diet produced distinct patterns of sex differences in
lipid levels compared with a chow diet, revealing the interaction of gonadal and
chromosomal sex with diet. Notably, under all dietary and gonadal conditions,
HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an
X and Y chromosome. By generating mice with XX, XY, and XXY chromosome
complements, we determined that the presence of 2 X chromosomes, and not the
absence of the Y chromosome, influences HDL-C concentration., We demonstrate
that having 2 X chromosomes versus an X and Y chromosome complement drives sex
differences in HDL-C. It is conceivable that increased expression of genes
escaping X-inactivation in XX mice regulates downstream processes to establish
sexual dimorphism in plasma lipid levels.




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