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Publication
Cholesteryl Ester Transfer Protein Impairs Triglyceride Clearance via Androgen
Receptor in Male Mice.
Authors Palmisano BT, Anozie U, Yu S, Neuman JC, Zhu L, Edington EM, Luu T, Stafford JM
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Lipids, References
Year 2020
Date Published 8/1/2020
Volume : Pages Not Specified : Not Specified
PubMed Reference 32783209
Abstract Elevated postprandial triacylglycerols (TAG) are an important risk factor for
cardiovascular disease. Men have higher plasma TAG and impaired TAG clearance
compared to women, which may contribute to sex differences in risk of
cardiovascular disease. Understanding mechanisms of sex differences in TAG
metabolism may yield novel therapeutic targets to prevent cardiovascular
disease. Cholesteryl ester transfer protein (CETP) is a lipid shuttling protein
known for its effects on high-density lipoprotein (HDL) cholesterol levels.
Although mice lack CETP, we previously demonstrated that transgenic CETP
expression in female mice alters TAG metabolism. The impact of CETP on TAG
metabolism in males, however, is not well understood. Here, we demonstrate that
CETP expression increases plasma TAG in males, especially in very-low density
lipoprotein (VLDL), by impairing postprandial plasma TAG clearance compared to
wild-type (WT) males. Gonadal hormones were required for CETP to impair TAG
clearance, suggesting a role for sex hormones for this effect. Testosterone
replacement in the setting of gonadectomy was sufficient to restore the effect
of CETP on TAG. Lastly, liver androgen receptor (AR) was required for CETP to
increase plasma TAG. Thus, expression of CETP in males raises plasma TAG by
impairing TAG clearance via testosterone signaling to AR. Further understanding
of how CETP and androgen signaling impair TAG clearance may lead to novel
approaches to reduce TAG and mitigate risk of cardiovascular disease.





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