Androgen Reduces Mitochondrial Respiration in Mouse Brown Adipocytes: A Model for Disordered Energy Balance in Polycystic Ovary Syndrome.
Androgen Reduces Mitochondrial Respiration in Mouse Brown Adipocytes: A Model for Disordered Energy Balance in Polycystic Ovary Syndrome.
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DOI：
10.3390/ijms22010243
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发表时间：
2020-12-29
影响因子：
5.6
通讯作者：
Franks S
中科院分区：
文献类型：
--
作者：
Lerner A;Kewada D;Ahmed A;Hardy K;Christian M;Franks S
多囊卵巢综合征 (PCOS) 是一种常见的内分泌疾病，与不良代谢特征相关，包括餐后产热减少。尽管多囊卵巢综合症女性脂肪组织功能异常已被广泛报道，但雄激素对白色脂肪细胞，特别是棕色脂肪细胞的直接影响知之甚少。本研究的目的是研究不可芳香化雄激素二氢睾酮 (DHT) 对 (1) 永生化小鼠棕色脂肪细胞系 (IMBAT) 中脂质积累和脂肪形成标记物表达、(2) IMBAT 中线粒体呼吸、(3) 线粒体 DNA 含量和基因表达、(4) 棕色脂肪组织 (BAT) 标记物表达和产热激活的影响。此外，我们还分析了 BAT 外植体分泌的 38 种脂肪因子的相对水平，并研究了雄激素对 IMBAT 和永生化小鼠白色脂肪 (IMWAT) 细胞系中脂肪因子基因表达的影响。雄激素治疗以剂量依赖性方式抑制 IMBAT 分化，减少脂肪生成标志物，并减弱 β-肾上腺素受体刺激的解偶联蛋白 1 (UCP1) 表达增加。在小鼠肩胛间 BAT 的外植体中，雄激素降低了 UCP1、过氧化物酶体增殖物激活受体-γ 共激活因子-1 (PCG-1) 和 Cidea 的表达。值得注意的是，通过 Seahorse XF 方法测量，雄激素处理不仅影响 BAT 中参与生热作用的基因，还减少了 IMBAT 中的线粒体呼吸。这项研究的结果表明，过量的雄激素在抑制棕色脂肪生成、减弱生热作用的激活和减少 BAT 中线粒体呼吸方面发挥着作用。总之，这些数据提供了一种可能导致多囊卵巢综合征女性餐后产热减少和肥胖倾向的合理分子机制。
Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with an adverse metabolic profile including reduced postprandial thermogenesis. Although abnormalities in adipose tissue function have been widely reported in women with PCOS, less is known about direct effects of androgen on white and, particularly, brown adipocytes. The purpose of this study was to investigate the effect of the nonaromatizable androgen dihydrotestosterone (DHT) on (1) lipid accumulation and expression of adipogenic markers in immortalized mouse brown adipose cell lines (IMBATs), (2) mitochondrial respiration in IMBATs, (3) mitochondrial DNA content and gene expression, (4) expression of brown adipose tissue (BAT) markers and thermogenic activation. In addition, we profiled the relative levels of 38 adipokines secreted from BAT explants and looked at androgen effects on adipokine gene expression in both IMBATs and immortalized mouse white adipose (IMWATs) cell lines. Androgen treatment inhibited IMBAT differentiation in a dose-dependent manner, reduced markers of adipogenesis, and attenuated the β-adrenoceptor-stimulated increase in uncoupling protein-1 (UCP1) expression. In explants of mouse interscapular BAT, androgen reduced expression of UCP1, peroxisome proliferator-activated receptor-γ coactivator-1 (PCG-1) and Cidea. Significantly, as well as affecting genes involved in thermogenesis in BAT, androgen treatment reduced mitochondrial respiration in IMBATs, as measured by the Seahorse XF method. The results of this study suggest a role for excess androgen in inhibiting brown adipogenesis, attenuating the activation of thermogenesis and reducing mitochondrial respiration in BAT. Together, these data provide a plausible molecular mechanism that may contribute to reduced postprandial thermogenesis and the tendency to obesity in women with PCOS.
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通讯作者：
López M