PDF(Pubmed)
Abstract：
BACKGROUND: Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with increased obesity, hyperandrogenism, and altered brown adipose tissue (BAT) thermogenesis. MicroRNAs play critical functions in brown adipocyte differentiation and maintenance. We aim to study the role of microRNA-21 (miR-21) in altered energy homeostasis and BAT thermogenesis in a PCOS mouse model of peripubertal androgen exposure.
METHODS: Three-week-old miR-21 knockout (miR21KO) or wild-type (WT) female mice were treated with dihydrotestosterone (DHT) or vehicle for 90 days. Body composition was determined by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) were measured by indirect calorimetry. Androgen receptor (AR), and markers of adipogenesis, de novo lipogenesis, angiogenesis, extracellular matrix remodeling, and thermogenesis were quantified by RT-qPCR and/or Western-blot.
RESULTS: MiR-21 ablation attenuated DHT-mediated increase in body weight while having no effect on fat or BAT mass. MiR-21 ablation attenuated DHT-mediated BAT AR upregulation. MiR-21 ablation did not alter EE; however, miR21KO DHT-treated mice have reduced VO2, VCO2, and RER. MiR-21 ablation reversed DHT-mediated decrease in food intake and increase in sleep time. MiR-21 ablation decreased some adipogenesis (Adipoq, Pparγ, and Cebpβ) and extracellular matrix remodeling (Mmp-9 and Timp-1) markers expression in DHT-treated mice. MiR-21 ablation abolished DHT-mediated increases in thermogenesis markers Cpt1a and Cpt1b, while decreasing CIDE-A expression.
CONCLUSIONS: Our findings suggest that BAT miR-21 may play a role in regulating DHT-mediated thermogenic dysfunction in PCOS. Modulation of BAT miR-21 levels could be a novel therapeutic approach for the treatment of PCOS-associated metabolic derangements.
Polycystic ovary syndrome (PCOS) is a common hormone disorder in premenopausal women, often linked to obesity and abnormal brown fat tissue activity. Women with PCOS have elevated male hormones, which are responsible for many metabolic problems. Our study focuses on understanding the role of microRNA-21 (miR-21) in the energy balance and brown fat tissue activity in a PCOS mouse model. We studied female mice with and without miR-21, treating them with a male hormone. We measured body composition and energy expenditure. We also analyzed the levels of specific genes and proteins related to fat tissue and energy production. Our findings showed that mice lacking miR-21 had less weight gain in response to male hormones, without fat or brown fat tissue mass changes. They also had reduced energy production, changed eating habits, and altered expression of genes related to fat tissue and energy production. In conclusion, our study suggests that miR-21 in brown fat tissue may regulate the energy imbalance caused by male hormones in PCOS. Adjusting miR-21 levels in brown fat tissue could be a new way to address the metabolic issues associated with PCOS.
METHODS: Three-week-old miR-21 knockout (miR21KO) or wild-type (WT) female mice were treated with dihydrotestosterone (DHT) or vehicle for 90 days. Body composition was determined by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) were measured by indirect calorimetry. Androgen receptor (AR), and markers of adipogenesis, de novo lipogenesis, angiogenesis, extracellular matrix remodeling, and thermogenesis were quantified by RT-qPCR and/or Western-blot.
RESULTS: MiR-21 ablation attenuated DHT-mediated increase in body weight while having no effect on fat or BAT mass. MiR-21 ablation attenuated DHT-mediated BAT AR upregulation. MiR-21 ablation did not alter EE; however, miR21KO DHT-treated mice have reduced VO2, VCO2, and RER. MiR-21 ablation reversed DHT-mediated decrease in food intake and increase in sleep time. MiR-21 ablation decreased some adipogenesis (Adipoq, Pparγ, and Cebpβ) and extracellular matrix remodeling (Mmp-9 and Timp-1) markers expression in DHT-treated mice. MiR-21 ablation abolished DHT-mediated increases in thermogenesis markers Cpt1a and Cpt1b, while decreasing CIDE-A expression.
CONCLUSIONS: Our findings suggest that BAT miR-21 may play a role in regulating DHT-mediated thermogenic dysfunction in PCOS. Modulation of BAT miR-21 levels could be a novel therapeutic approach for the treatment of PCOS-associated metabolic derangements.
Polycystic ovary syndrome (PCOS) is a common hormone disorder in premenopausal women, often linked to obesity and abnormal brown fat tissue activity. Women with PCOS have elevated male hormones, which are responsible for many metabolic problems. Our study focuses on understanding the role of microRNA-21 (miR-21) in the energy balance and brown fat tissue activity in a PCOS mouse model. We studied female mice with and without miR-21, treating them with a male hormone. We measured body composition and energy expenditure. We also analyzed the levels of specific genes and proteins related to fat tissue and energy production. Our findings showed that mice lacking miR-21 had less weight gain in response to male hormones, without fat or brown fat tissue mass changes. They also had reduced energy production, changed eating habits, and altered expression of genes related to fat tissue and energy production. In conclusion, our study suggests that miR-21 in brown fat tissue may regulate the energy imbalance caused by male hormones in PCOS. Adjusting miR-21 levels in brown fat tissue could be a new way to address the metabolic issues associated with PCOS.
摘要：
背景：多囊卵巢综合征（PCOS），绝经前妇女最常见的内分泌紊乱,与肥胖增加有关，雄激素过多症,和改变棕色脂肪组织（BAT）产热。MicroRNAs在棕色脂肪细胞分化和维持中发挥重要作用。我们旨在研究microRNA-21（miR-21）在青春期雄激素暴露的PCOS小鼠模型中能量稳态和BAT产热改变中的作用。
方法:用二氢睾酮(DHT)或载体处理三周龄miR-21敲除(miR21KO)或野生型(WT)雌性小鼠90天。通过EchoMRI确定身体成分。能源支出（EE），耗氧量（VO2），二氧化碳产量(VCO2)，和呼吸交换比（RER）通过间接量热法测量。雄激素受体(AR),和脂肪形成的标记，从头脂肪生成，血管生成,细胞外基质重塑，和产热通过RT-qPCR和/或Western印迹定量。
结果：MiR-21消融减弱了DHT介导的体重增加，而对脂肪或BAT质量没有影响。MiR-21消融减弱DHT介导的BATAR上调。MiR-21消融并未改变EE;然而,miR21KODHT处理的小鼠具有降低的VO2、VCO2和RER。MiR-21消融逆转了DHT介导的食物摄入减少和睡眠时间增加。MiR-21消融减少了一些脂肪生成(Adipoq，pparγ,在DHT处理的小鼠中，Cebpβ）和细胞外基质重塑（Mmp-9和Timp-1）标志物的表达。MiR-21消融消除了DHT介导的产热标志物Cpt1a和Cpt1b的增加，同时降低CIDE-A表达式。
结论：我们的研究结果表明，BATmiR-21可能在调节PCOS中DHT介导的产热功能障碍中发挥作用。调节BATmiR-21水平可能是治疗PCOS相关代谢紊乱的一种新的治疗方法。
多囊卵巢综合征（PCOS）是绝经前妇女常见的激素紊乱，通常与肥胖和棕色脂肪组织活动异常有关。患有PCOS的女性男性荷尔蒙升高，这是许多代谢问题的原因。我们的研究重点是了解microRNA-21（miR-21）在PCOS小鼠模型中能量平衡和棕色脂肪组织活性中的作用。我们研究了有和没有miR-21的雌性小鼠，用雄性激素治疗它们。我们测量了身体成分和能量消耗。我们还分析了与脂肪组织和能量产生相关的特定基因和蛋白质的水平。我们的发现表明，缺乏miR-21的小鼠响应雄性激素的体重增加较少，无脂肪或棕色脂肪组织质量变化。他们还减少了能源生产，改变饮食习惯，和改变与脂肪组织和能量产生相关的基因的表达。总之,我们的研究表明，棕色脂肪组织中的miR-21可能调节PCOS中由雄性激素引起的能量失衡。调节棕色脂肪组织中的miR-21水平可能是解决与PCOS相关的代谢问题的新方法。
方法:用二氢睾酮(DHT)或载体处理三周龄miR-21敲除(miR21KO)或野生型(WT)雌性小鼠90天。通过EchoMRI确定身体成分。能源支出（EE），耗氧量（VO2），二氧化碳产量(VCO2)，和呼吸交换比（RER）通过间接量热法测量。雄激素受体(AR),和脂肪形成的标记，从头脂肪生成，血管生成,细胞外基质重塑，和产热通过RT-qPCR和/或Western印迹定量。
结果：MiR-21消融减弱了DHT介导的体重增加，而对脂肪或BAT质量没有影响。MiR-21消融减弱DHT介导的BATAR上调。MiR-21消融并未改变EE;然而,miR21KODHT处理的小鼠具有降低的VO2、VCO2和RER。MiR-21消融逆转了DHT介导的食物摄入减少和睡眠时间增加。MiR-21消融减少了一些脂肪生成(Adipoq，pparγ,在DHT处理的小鼠中，Cebpβ）和细胞外基质重塑（Mmp-9和Timp-1）标志物的表达。MiR-21消融消除了DHT介导的产热标志物Cpt1a和Cpt1b的增加，同时降低CIDE-A表达式。
结论：我们的研究结果表明，BATmiR-21可能在调节PCOS中DHT介导的产热功能障碍中发挥作用。调节BATmiR-21水平可能是治疗PCOS相关代谢紊乱的一种新的治疗方法。
多囊卵巢综合征（PCOS）是绝经前妇女常见的激素紊乱，通常与肥胖和棕色脂肪组织活动异常有关。患有PCOS的女性男性荷尔蒙升高，这是许多代谢问题的原因。我们的研究重点是了解microRNA-21（miR-21）在PCOS小鼠模型中能量平衡和棕色脂肪组织活性中的作用。我们研究了有和没有miR-21的雌性小鼠，用雄性激素治疗它们。我们测量了身体成分和能量消耗。我们还分析了与脂肪组织和能量产生相关的特定基因和蛋白质的水平。我们的发现表明，缺乏miR-21的小鼠响应雄性激素的体重增加较少，无脂肪或棕色脂肪组织质量变化。他们还减少了能源生产，改变饮食习惯，和改变与脂肪组织和能量产生相关的基因的表达。总之,我们的研究表明，棕色脂肪组织中的miR-21可能调节PCOS中由雄性激素引起的能量失衡。调节棕色脂肪组织中的miR-21水平可能是解决与PCOS相关的代谢问题的新方法。
