PDF(Pubmed)
Abstract：
Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs\' proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.
摘要：
肥胖会导致多个器官的代谢改变，强调器官间通信在其发病机制中的作用。细胞外囊泡（EV）是生理和病理条件下的通讯剂，尽管它们与肥胖合并症有关，在这种情况下，它们的蛋白质货物在很大程度上仍然未知。要破译电动汽车中封装的消息，我们从饮食诱导的肥胖小鼠模型中分离血浆来源的EV.肥胖血浆EV显示蛋白质多样性下降，而对照EV显示蛋白质折叠功能显着富集，强调正确折叠在维持代谢稳态中的重要性。以前,我们发现肠道衍生的电动汽车蛋白质组对肥胖具有特殊的意义。这里,我们比较了血浆和肠道电动汽车，并确定了四种蛋白质在两种电动汽车的对照状态下完全存在，通过分析血液来源的电动汽车，揭示了对肠道健康进行非侵入性评估的潜力。鉴于翻译后修饰（PTM）的相关性，我们观察到在肥胖的肠道电动汽车中染色质相关蛋白从糖化到乙酰化的转变，提示肥胖期间靶向DNA转录的调节机制。这项研究为电动汽车和蛋白质PTM在肥胖背后的复杂机制中的新作用提供了有价值的见解。为未来的研究提供潜在的生物标志物和途径。
