Jones M E, Thorburn A W, Britt K L, Hewitt K N, Misso M L, Wreford N G, Proietto J, Oz O K, Leury B J, Robertson K M, Yao S, Simpson E R
Prince Henry's Institute of Medical Research, P.O. Box 5152, Vic. 3168, Clayton, Australia.
J Steroid Biochem Mol Biol. 2001 Dec;79(1-5):3-9. doi: 10.1016/s0960-0760(01)00136-4.
Aromatase is the enzyme which catalyses the conversion of C19 steroids into C18 estrogens. We have generated a mouse model wherein the Cyp19 gene, which encodes aromatase, has been disrupted, and hence, the aromatase knockout (ArKO) mouse cannot synthesise endogenous estrogens. We examined the consequences of estrogen deficiency on accumulation of adipose depots in male and female ArKO mice, observing that these animals progressively accrue significantly more intra-abdominal adipose tissue than their wildtype (WT) litter mates, reflected in increased adipocyte volume and number. This increased adiposity was not due to hyperphagia or reduced resting energy expenditure, but was associated with reduced spontaneous physical activity levels, reduced glucose oxidation, and a decrease in lean body mass. Elevated circulating levels of leptin and cholesterol were present in 1-year-old ArKO mice compared to WT controls, as were elevated insulin levels, although blood glucose was unchanged. Associated with these changes, the livers of ArKO animals were characterised by a striking accumulation of lipid droplets. Our findings demonstrate an important role for estrogen in the maintenance of lipid homeostasis in both males and females.
芳香化酶是一种催化C19类固醇转化为C18雌激素的酶。我们构建了一种小鼠模型，其中编码芳香化酶的Cyp19基因已被破坏，因此，芳香化酶基因敲除（ArKO）小鼠无法合成内源性雌激素。我们研究了雌激素缺乏对雄性和雌性ArKO小鼠脂肪库积累的影响，观察到这些动物比其野生型（WT）同窝小鼠逐渐积累了更多的腹部内脂肪组织，这表现为脂肪细胞体积和数量增加。这种肥胖增加并非由于摄食过多或静息能量消耗减少，而是与自发身体活动水平降低、葡萄糖氧化减少以及瘦体重下降有关。与WT对照组相比，1岁的ArKO小鼠循环中瘦素和胆固醇水平升高，胰岛素水平也升高，尽管血糖未变。与这些变化相关的是，ArKO动物的肝脏以脂质小滴的显著积累为特征。我们的研究结果表明雌激素在维持雄性和雌性脂质稳态中起着重要作用。
