Aims

The purpose of the study is to explore the mechanism of transdifferentiation from white adipose tissue (WAT) to Brown adipose tissue (BAT).

Materials and method

In this study, we established a model of mouse obesity induced by a high-fat diet (HFD) before 30 days of forced exercise or sedentary mice. Then, we isolated extracellular vesicles (EVs) from plasma and identified them by transmission electron microscope, dynamic light scattering and western blot analysis. Body temperature and body weight were utilized for assessment of thermogenesis in vivo. Oil red O staining was used to measure triglyceride in vitro. Luciferase reporter assay was applied for the relationship between miR-191a-5p and Prdm16.

Key findings

As a result, mice that exercised for a long period time exhibited higher caloric expenditure, better weight maintenance and more WAT browning, as well as better resistance to obesity associated with a high-fat diet, compared to mice that lacked exercise. MircoRNA-191-5p (miR-191-5p) was found to be lowly expressed in the EVs from mice with long-term exercise (Exe-EVs). Functional experiments revealed that Exe-EVs promoted WAT browning by the silencing of miR-191-5p. At the molecular level, siRNA-mediated PRDM16 partly inhibited uncoupling protein-1(UCP-1) expression by miR-191-5p inhibitor in white adipocytes. Here, we observed that the lowly expressed miR-191-5p in Exe-EVs promoted the browning of WAT by negatively targeting the PRDM16-3′-untranslated region (PRDM16-3′UTR), thereby enhancing heat production and reducing obesity.

Significance

MiR-191-5p may serve as a potential target for the identification and treatment of obesity.

中文翻译：

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长期运动分泌的细胞外囊泡通过抑制miR-191a-5p促进白色脂肪细胞褐变。

目的

该研究的目的是探讨从白色脂肪组织（WAT）到棕色脂肪组织（BAT）的转分化机制。

材料与方法

在这项研究中，我们建立了强制运动或久坐小鼠30天前由高脂饮食（HFD）诱发的小鼠肥胖模型。然后，我们从血浆中分离出细胞外囊泡（EVs），并通过透射电子显微镜，动态光散射和Western blot分析鉴定它们。体温和体重用于评估体内生热。油红O染色用于体外测量甘油三酸酯。萤光素酶报告基因检测用于miR-191a-5p和Prdm16之间的关系。

主要发现

结果，与缺乏运动的小鼠相比，长时间运动的小鼠表现出更高的卡路里消耗，更好的体重维持和更多的WAT褐变，以及对与高脂饮食相关的肥胖症的更好抵抗力。发现长期运动小鼠（Exe-EV）的EV中MircoRNA-191-5p（miR-191-5p）低表达。功能实验表明，Exe-EV通过沉默miR-191-5p促进WAT褐变。在分子水平上，siRNA介导的PRDM16通过miR-191-5p抑制剂部分抑制白色脂肪细胞中的解偶联蛋白1（UCP-1）表达。在这里，我们观察到在Exe-EV中低表达的miR-191-5p通过负向靶向PRDM16-3'-非翻译区（PRDM16-3'UTR）促进WAT褐变，从而增强热量产生并减少肥胖。

意义

MiR-191-5p可能会成为肥胖症识别和治疗的潜在靶标。