ERα regulates lipid metabolism in bone through ATGL and perilipin.

ERα regulates lipid metabolism in bone through ATGL and perilipin.
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DOI:
10.1002/jcb.24470
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发表时间:
2013-06
影响因子:
4
通讯作者:
Krum SA
Krum SA
中科院分区:
生物学2区
文献类型:
--
作者:
Wend K;Wend P;Drew BG;Hevener AL;Miranda-Carboni GA;Krum SA

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绝经期骨密度的降低伴随着骨髓间隙中脂肪细胞的增加。卵巢切除术也会导致脂肪在骨髓中积聚。在此,我们显示与野生型(WT)小鼠或雌激素受体β(ERβ)敲除(ER βKO)小鼠相比,雌激素受体α(ERα)敲除(ERαKO)小鼠骨髓中的脂质蓄积增加。同样,与WT小鼠或ERβKO小鼠的细胞相比,ERαKO小鼠的骨髓细胞在培养中分化为脂肪细胞也具有增加的脂质蓄积。单个脂肪细胞的分析显示,WT小鼠每个细胞的脂滴比ERαKO或ERβKO动物的脂肪细胞少,但更大。此外,WT脂肪细胞中较高水平的脂肪甘油三酯脂肪酶(ATGL)蛋白与脂解增加和每个细胞较少的脂滴相关,17β-雌二醇(E2)处理增强了这种反应。相比之下,ERαKO小鼠的细胞显示更高的周脂蛋白水平,促进脂肪生成。总之,这些结果表明,E2通过ERα信号调节体内骨髓空间中的脂滴大小和总脂质蓄积。
A decrease in bone mineral density during menopause is accompanied by an increase in adipocytes in the bone marrow space. Ovariectomy also leads to accumulation of fat in the bone marrow. Herein we show increased lipid accumulation in bone marrow from estrogen receptor alpha (ERα) knockout (ERαKO) mice compared to wild-type (WT) mice or estrogen receptor beta (ERβ) knockout (ERβKO) mice. Similarly, bone marrow cells from ERαKO mice differentiated to adipocytes in culture also have increased lipid accumulation compared to cells from WT mice or ERβKO mice. Analysis of individual adipocytes shows that WT mice have fewer, but larger, lipid droplets per cell than adipocytes from ERαKO or ERβKO animals. Furthermore, higher levels of adipose triglyceride lipase (ATGL) protein in WT adipocytes correlate with increased lipolysis and fewer lipid droplets per cell and treatment with 17β-estradiol (E2) potentiates this response. In contrast, cells from ERαKO mice display higher perilipin protein levels, promoting lipogenesis. Together these results demonstrate that E2 signals via ERα to regulate lipid droplet size and total lipid accumulation in the bone marrow space in vivo.
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