Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice
Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice
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DOI：
10.1016/j.abb.2017.03.007
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发表时间：
2017-05-15
影响因子：
3.9
通讯作者：
Ishigami, Akihito
中科院分区：
文献类型：
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作者：
Amano, Akiko;Kondo, Yoshitaka;Ishigami, Akihito
性类固醇激素，例如雌激素和睾酮，被认为在脂质代谢中发挥重要作用。为了阐明雌激素消耗对雄性和雌性小鼠脂质代谢的影响，我们使用了芳香酶敲除 (ArKO) 小鼠，其中 Cyp19 基因破坏阻止了体内雌激素的合成。这些小鼠被分为以下 4 组：雄性和雌性 ArKO 小鼠以及雄性和雌性野生型 (WT) 小鼠。这些小鼠随意喂食正常脂肪饮食（13.6%脂肪）。出生后159天，检测小鼠的肝脏和血浆脂质含量以及肝激素受体和脂质/脂蛋白代谢相关基因的表达。有趣的是，我们发现雄性 ArKO 小鼠的肝脏脂肪变性伴随着血浆睾酮水平显着升高，但雌性 ArKO 小鼠则不然。雄性 ArKO 小鼠的血浆脂蛋白谱显示 LDL 和小密度 LDL 甘油三酯 (TG) 水平同时降低。此外，雄性小鼠（而非雌性小鼠）的雄激素受体（AR）、甾醇调节元件结合蛋白 I（SREBP1）和 CD36 表达显着升高。这些结果强烈表明，Cyp19 基因破坏会诱发雄性小鼠的性二态性反应和高血浆睾酮水平，也会诱发肝脂肪变性。 (C) 2017 Elsevier Inc. 保留所有权利。
Sex steroid hormones, such as estrogen and testosterone, are believed to play important roles in lipid metabolism. To elucidate the effects of estrogen depletion on lipid metabolism in male and female mice, we used aromatase-knockout (ArKO) mice, in which Cyp19 gene disruption prevented estrogen synthesis in vivo. These mice were divided into the following 4 groups: male and female ArKO mice and male and female wild-type (WT) mice. These mice were fed a normal-fat diet (13.6% fat) ad libitum. At 159 days after birth, the mice were tested for liver and plasma lipid content and hepatic hormone receptor and lipid/lipoprotein metabolism-related gene expression. Interestingly, we found that hepatic steatosis was accompanied by markedly elevated plasma testosterone levels in male ArKO mice but not in female ArKO mice. Plasma lipoprotein profiles exhibited concurrent decreases in LDL- and small dense LDL-triglyceride (TG) levels in male ArKO mice. Moreover, male mice, but not female mice, exhibited marked elevations in androgen receptor (AR), sterol regulatory element-binding protein I (SREBP1), and CD36 expression. These results strongly suggest that Cyp19 gene disruption, which induces a sexually dimorphic response and high plasma testosterone levels in male mice, also induces hepatic steatosis. (C) 2017 Elsevier Inc. All rights reserved.