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Adipocyte-derived extracellular vesicles modulate appetite and weight through mTOR signalling in the hypothalamus.
Acta Physiologica ( IF 5.6 ) Pub Date : 2019-07-27 , DOI: 10.1111/apha.13339
Jie Gao 1 , Xinyu Li 1 , You Wang 2 , Yan Cao 1 , Dengju Yao 3 , Lijie Sun 1 , Lv Qin 1 , Hui Qiu 1 , Xiaorong Zhan 1
Affiliation  

AIM Type 2 diabetes and obesity are diseases related to surplus energy in the body. Abnormal interaction between the hypothalamus and adipose tissues is a key trigger of energy metabolism dysfunction. Extracellular vesicles (EVs) regulate intercellular communication by transporting intracellular cargo to recipient cells thereby altering the function of recipient cells. This study aimed to evaluate whether adipocyte-derived EVs can act on hypothalamic neurons to modulate energy intake and to identify the EV-associated non-coding RNAs. METHODS Confocal imaging was used to trace the uptake of labelled adipocyte-derived exosomes by hypothalamic anorexigenic POMC neurons. The effects of adipocyte-derived EVs on the mammalian target of rapamycin (mTOR) signalling pathway in POMC neurons were evaluated based on mRNA and protein expression in vitro using quantitative real-time PCR and western blotting. In addition, adipocyte-derived EVs were injected into recipient mice, and changes in mice body weight and daily food intake were monitored. The biological effects of the EV-associated MALAT1 on POMC neurons were explored. RESULTS Adipocyte-derived EVs were successfully transferred into POMC neurons in vitro. Results showed that adipocytes of obese mice secreted MALAT1-containing EVs, which increased appetite and weight when administered to lean mice. Conversely, adipocyte-derived EVs from lean mice decreased food intake and weight when administered to obese mice. CONCLUSION Adipocyte-derived EVs play important roles in mediating the interaction between adipocytes and hypothalamic neurons. Adipocyte-derived EVs can regulate POMC expression through the hypothalamic mTOR signalling in vivo and in vitro, thereby affecting body energy intake.

中文翻译:

脂肪细胞衍生的细胞外小泡通过下丘脑中的mTOR信号传导调节食欲和体重。

AIM 2型糖尿病和肥胖症是与体内多余能量有关的疾病。下丘脑和脂肪组织之间的异常相互作用是能量代谢功能障碍的关键触发因素。细胞外囊泡(EVs)通过将细胞内货物运输到受体细胞来调节细胞间的通讯,从而改变受体细胞的功能。这项研究旨在评估脂肪细胞衍生的电动汽车是否可以作用于下丘脑神经元,从而调节能量的摄入并确定与电动汽车相关的非编码RNA。方法使用共聚焦成像法来追踪下丘脑厌食性POMC神经元对标记的脂肪细胞来源的外泌体的摄取。使用定量实时PCR和Western印迹,基于mRNA和蛋白表达,评估了脂肪细胞衍生的EV对POMC神经元中雷帕霉素(mTOR)信号转导途径的哺乳动物靶标的影响。此外,将脂肪细胞源的电动汽车注射到受体小鼠体内,并监测小鼠体重和每日食物摄入量的变化。探索了EV相关的MALAT1对POMC神经元的生物学作用。结果脂肪细胞源性电动汽车已成功地转移到POMC神经元的体外。结果表明,肥胖小鼠的脂肪细胞分泌含MALAT1的电动汽车,当向瘦小鼠服用时,它们会增加食欲和体重。相反,当给肥胖小鼠服用时,来自瘦小鼠的脂肪细胞衍生的电动汽车减少了食物摄入和体重。结论源自脂肪细胞的电动汽车在介导脂肪细胞与下丘脑神经元之间的相互作用中起重要作用。源自脂肪细胞的电动汽车可通过下丘脑mTOR信号在体内和体外调节POMC的表达,从而影响人体的能量摄入。
更新日期:2019-11-18
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