Elevated plasma triglycerides (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 triglyceride metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, but not in non-transgenic littermate females. This increase in plasma TGs in response to estrogen was due to increased TG production and increased expression and activity of genes involved in Very-Low Density Lipoprotein (VLDL) synthesis and assembly. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased plasma metabolites of liver β-oxidation, increased expression of liver genes involved in â-oxidation, and reduced liver TG content by 60% relative to non-transgenic littermate females. Thus, CETP is required for the hypertriglyceridemic effects of estrogen in female mice. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism.
|Advisor:||Hasty, Alyssa H.|
|Commitee:||Hasty, Alyssa H., McGuinness, Owen P., Stafford, John M., Swift, Larry L.|
|Department:||Molecular Physiology and Biophysics|
|School Location:||United States -- Tennessee|
|Source:||DAI-B 80/08(E), Dissertation Abstracts International|
|Keywords:||Ester transfer, Liver, Transgenic mice|
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