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Publication
Cholesteryl ester transfer protein alters liver and plasma triglyceride
metabolism through two liver networks in female mice.
Authors Palmisano BT, Le TD, Zhu L, Lee YK, Stafford JM
Submitted By Submitted Externally on 10/26/2016
Status Published
Journal Journal of lipid research
Year 2016
Date Published
Volume : Pages 57 : 1541 - 51
PubMed Reference 27354419
Abstract Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen
treatment raises plasma TGs in women, but molecular mechanisms remain poorly
understood. Here we explore the role of cholesteryl ester transfer protein
(CETP) in the regulation of TG metabolism in female mice, which naturally lack
CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs
50%, increased TG production, and increased expression of genes involved in VLDL
synthesis, but not in nontransgenic littermate females. In CETP females,
estrogen enhanced expression of small heterodimer partner (SHP), a nuclear
receptor regulating VLDL production. Deletion of liver SHP prevented increases
in TG production and expression of genes involved in VLDL synthesis in CETP mice
with estrogen treatment. We also examined whether CETP expression had effects on
TG metabolism independent of estrogen treatment. CETP increased liver
ß-oxidation and reduced liver TG content by 60%. Liver estrogen receptor a (ERa)
was required for CETP expression to enhance ß-oxidation and reduce liver TG
content. Thus, CETP alters at least two networks governing TG metabolism, one
involving SHP to increase VLDL-TG production in response to estrogen, and
another involving ERa to enhance ß-oxidation and lower liver TG content. These
findings demonstrate a novel role for CETP in estrogen-mediated increases in TG
production and a broader role for CETP in TG metabolism.






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