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Aromatase deficiency in hematopoietic cells improves glucose tolerance in male mice through skeletal muscle-specific effects.
PLOS ONE ( IF 3.7 ) Pub Date : 2020-01-23 , DOI: 10.1371/journal.pone.0227830
Katya B Rubinow 1 , Laura J den Hartigh 1 , Leela Goodspeed 1 , Shari Wang 1 , Orhan K Oz 2
Affiliation  

Estrogens are important for maintaining metabolic health in males. However, the key sources of local estrogen production for regulating energy metabolism have not been fully defined. Immune cells exhibit aromatase activity and are resident in metabolic tissues. To determine the relative contribution of immune cell-derived estrogens for metabolic health in males, C57BL6/J mice underwent bone marrow transplant with marrow from either wild-type (WT(WT)) or aromatase-deficient (WT(ArKO)) donors. Body weight, body composition, and glucose and insulin tolerance were assessed over 24 weeks with mice maintained on a regular chow diet. No differences were found in insulin sensitivity between groups, but WT(ArKO) mice were more glucose tolerant than WT(WT) mice 20 weeks after transplant, suggestive of enhanced glucose disposal (AUCglucose 6061±3349 in WT(WT) mice versus 3406±1367 in WT(ArKO) mice, p = 0.01). Consistent with this, skeletal muscle from WT(ArKO) mice showed higher expression of the mitochondrial genes Ppargc1a (p = 0.03) and Nrf1 (p = 0.01), as well as glucose transporter type 4 (GLUT4, Scl2a4; p = 0.02). Skeletal muscle from WT(ArKO) mice had a lower concentration of 17β-estradiol (5489±2189 pg/gm in WT(WT) mice versus 3836±2160 pg/gm in WT(ArKO) mice, p = 0.08) but higher expression of estrogen receptor-α (ERα, Esr1), raising the possibility that aromatase deficiency in immune cells led to a compensatory increase in ERα signaling. No differences between groups were found with regard to body weight, adiposity, or gene expression within adipose tissue or liver. Immune cells are a key source of local 17β-estradiol production and contribute to metabolic regulation in males, particularly within skeletal muscle. The respective intracrine and paracrine roles of immune cell-derived estrogens require further delineation, as do the pathways that regulate aromatase activity in immune cells specifically within metabolic tissues.

中文翻译:

造血细胞中的芳香化酶缺乏症通过骨骼肌特异性作用改善了雄性小鼠的葡萄糖耐量。

雌激素对于维持男性的代谢健康很重要。但是,尚未完全确定用于调节能量代谢的局部雌激素产生的关键来源。免疫细胞表现出芳香化酶活性,并驻留在代谢组织中。为了确定雄性免疫细胞源性雌激素对代谢健康的相对贡献,对C57BL6 / J小鼠进行了骨髓移植,其中包括野生型(WT(WT))或芳香酶缺乏型(WT(ArKO))供体的骨髓移植。在24周的常规饮食中对小鼠的体重,身体组成以及葡萄糖和胰岛素耐受性进行了评估。两组之间的胰岛素敏感性没有差异,但是移植后20周,WT(ArKO)小鼠比WT(WT)小鼠对葡萄糖的耐受性更高,提示葡萄糖处置增强(WT(WT)小鼠为AUCglucose 6061±3349,而WT(ArKO)小鼠为3406±1367,p = 0.01)。与此相一致,来自WT(ArKO)小鼠的骨骼肌显示线粒体基因Ppargc1a(p = 0.03)和Nrf1(p = 0.01)以及4型葡萄糖转运蛋白(GLUT4,Scl2a4; p = 0.02)的更高表达。WT(ArKO)小鼠的骨骼肌17β-雌二醇浓度较低(WT(WT)小鼠为5489±2189 pg / gm,而WT(ArKO)小鼠为3836±2160 pg / gm,p = 0.08),但表达较高雌激素受体-α(ERα,Esr1)的表达,增加了免疫细胞中芳香化酶缺乏导致ERα信号代偿性增加的可能性。两组之间在体重,肥胖或脂肪组织或肝脏内的基因表达方面没有差异。免疫细胞是局部产生17β-雌二醇的关键来源,有助于男性,特别是骨骼肌内的代谢调节。免疫细胞衍生的雌激素各自的内分泌和旁分泌作用需要进一步描述,调节免疫细胞中芳香化酶活性的途径特别是在代谢组织中的途径也需要进一步描述。
更新日期:2020-01-24
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