Precision medicine is still not considered as a standard of care in obesity treatment, despite a large heterogeneity in the metabolic phenotype of individuals with obesity. One of the strongest factors influencing the variability in metabolic disease risk is adipose tissue (AT) dysfunction; however, there is little understanding of the link between distinct cell populations, cell-type-specific transcriptional programs, and disease severity. Here, we generated a comprehensive cellular map of subcutaneous and visceral AT of individuals with metabolically healthy and unhealthy obesity. By combining single-nucleus RNA-sequencing data with bulk transcriptomics and clinical parameters, we identified that mesothelial cells, adipocytes, and adipocyte-progenitor cells exhibit the strongest correlation with metabolic disease. Furthermore, we uncovered cell-specific transcriptional programs, such as the transitioning of mesothelial cells to a mesenchymal phenotype, that are involved in uncoupling obesity from metabolic disease. Together, these findings provide valuable insights by revealing biological drivers of clinical endpoints.

中文翻译：

---

揭示与肥胖代谢健康相关的脂肪种群


尽管肥胖个体的代谢表型存在很大异质性，但精准医学仍未被视为肥胖治疗的护理标准。影响代谢疾病风险变异性的最强因素之一是脂肪组织 （AT） 功能障碍;然而，人们对不同细胞群、细胞类型特异性转录程序和疾病严重程度之间的联系知之甚少。在这里，我们生成了代谢健康和不健康肥胖个体皮下和内脏 AT 的综合细胞图谱。通过将单核 RNA 测序数据与大量转录组学和临床参数相结合，我们发现间皮细胞、脂肪细胞和脂肪细胞祖细胞与代谢疾病的相关性最强。此外，我们发现了细胞特异性转录程序，例如间皮细胞向间充质表型的转变，这些程序与肥胖与代谢疾病的解偶联有关。总之，这些发现通过揭示临床终点的生物学驱动因素提供了有价值的见解。