Cholesteryl Ester Transfer Protein Impairs Triglyceride Clearance via Androgen Receptor in Male Mice.
Cholesteryl Ester Transfer Protein Impairs Triglyceride Clearance via Androgen Receptor in Male Mice.
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DOI：
10.1002/lipd.12271
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发表时间：
2021-01
期刊：
影响因子：
1.9
通讯作者：
Stafford JM
中科院分区：
文献类型：
--
作者：
Palmisano BT;Anozie U;Yu S;Neuman JC;Zhu L;Edington EM;Luu T;Stafford JM
餐后甘油三酯（TAG）升高是心血管疾病的重要危险因素。与女性相比，男性的血浆TAG更高，TAG清除率受损，这可能导致心血管疾病风险的性别差异。了解TAG代谢的性别差异机制可能会产生新的治疗靶点，以预防心血管疾病。胆固醇酯转移蛋白（CETP）是一种脂质穿梭蛋白，因其对高密度脂蛋白（HDL）胆固醇水平的影响而闻名。虽然小鼠缺乏CETP，我们以前证明，转基因CETP表达在雌性小鼠改变TAG代谢。然而，CETP对男性TAG代谢的影响尚不清楚。在这里，我们证明了与野生型（WT）男性相比，CETP表达通过损害餐后血浆TAG清除率来增加男性的血浆TAG，特别是极低密度脂蛋白（VLDL）。CETP需要性腺激素来损害TAG清除，这表明性激素在这种作用中的作用。在性腺切除术的情况下，替吉奥替代足以恢复CETP对TAG的作用。最后，CETP需要肝脏雄激素受体（AR）来增加血浆TAG。因此，CETP在雄性中的表达通过经由睾酮信号传导至AR而损害TAG清除来提高血浆TAG。进一步了解CETP和雄激素信号传导如何损害TAG清除可能会导致新的方法来减少TAG和降低心血管疾病的风险。
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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影响因子：
37.8
作者：
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通讯作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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