Maternal hypercholesterolemia leads to activation of endogenous cholesterol synthesis in the offspring.
OBJECTIVE
The purpose of this study was to determine the effect of maternal hypercholesterolemia on hepatic cholesterol metabolism in the offspring in a mouse model.


METHODS
Male and female wild type and apoE(-/-KO) (knockout for the apoprotein E [apoE]) gene) mice were crossbred to obtain all 4 possible genetic offspring types. The litters were maintained on regular chow and sacrificed at 8 months of age. Liver samples were collected and the mRNA expression levels for SCAP, SREBP-1a, SREBP-2, HMGCR, and LDLR determined using real-time RT-PCR.


RESULTS
We found a significant activation of the transcriptional activity of genes involved in endogenous cholesterol synthesis, as well as LDLR, in the liver of adult mice born to hypercholesterolemic dams.


CONCLUSIONS
Reprogramming of hepatic cholesterol homeostasis may be the basis for an increased predisposition to hypercholesterolemia and atherosclerosis found in offspring of mice exposed to a high cholesterol environment during early life.
Goharkhay
Nima
N
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
Tamayo
Esther H
EH
Yin
Huaizhi
H
Hankins
Gary D V
GD
Saade
George R
GR
Longo
Monica
M
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006937:Hypercholesterolemia / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000032:analysis; D051782:Sterol Regulatory Element Binding Protein 2 / Q000032:analysis
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C102196:SREBP cleavage-activating protein; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol
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