Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.

Title

Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.

Creator

Palmisano Brian T; Le Thao D; Zhu Lin; Lee Yoon-Kwang; Stafford John M

Publisher

Journal of lipid research

Date

2016
2016-08

Description

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 beta-oxidation and reduced liver TG content by 60%. Liver estrogen receptor alpha (ERalpha) was required for CETP expression to enhance beta-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 ERalpha to enhance beta-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.

Subject

*estrogen; *estrogen receptor alpha; *lipid and lipoprotein metabolism; *small heterodimer partner; *triglycerides; *very low density lipoprotein; Animals; Cholesterol Ester Transfer Proteins/*physiology; Estrogen Receptor alpha/metabolism; Estrogens/physiology; Female; Inbred C57BL; Lipid Metabolism; Liver/*metabolism; Metabolic Networks and Pathways; Mice; Oxidation-Reduction; Transgenic; Triglycerides/biosynthesis/*blood

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1541–1551

Issue

8

Volume

57

Citation

Palmisano Brian T; Le Thao D; Zhu Lin; Lee Yoon-Kwang; Stafford John M, “Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.,” NEOMED Bibliography Database, accessed September 19, 2021, https://neomed.omeka.net/items/show/4878.

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