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Publication
Low-density lipoprotein receptor is required for cholesteryl ester transfer
protein to regulate triglyceride metabolism in both male and female mice.
Authors Palmisano BT, Yu S, Neuman JC, Zhu L, Luu T, Stafford JM
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Physiological reports
Year 2021
Date Published 2/1/2021
Volume : Pages 9 : e14732
PubMed Reference 33625789
Abstract Elevated triglycerides (TGs) and impaired TG clearance increase the risk of
cardiovascular disease in both men and women, but molecular mechanisms remain
poorly understood. Cholesteryl ester transfer protein (CETP) is a lipid
shuttling protein known for its effects on high-density lipoprotein cholesterol.
Although mice lack CETP, transgenic expression of CETP in mice alters TG
metabolism in males and females by sex-specific mechanisms. A unifying mechanism
explaining how CETP alters TG metabolism in both males and females remains
unknown. Since low-density lipoprotein receptor (LDLR) regulates both TG
clearance and very low density lipoprotein (VLDL) production, LDLR may be
involved in CETP-mediated alterations in TG metabolism in both males and
females. We hypothesize that LDLR is required for CETP to alter TG metabolism in
both males and females. We used LDLR null mice with and without CETP to
demonstrate that LDLR is required for CETP to raise plasma TGs and to impair TG
clearance in males. We also demonstrate that LDLR is required for CETP to
increase TG production and to increase the expression and activity of VLDL
synthesis targets in response to estrogen. Additionally, we show that LDLR is
required for CETP to enhance ß-oxidation. These studies support that LDLR is
required for CETP to regulate TG metabolism in both males and females.




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