Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655,USA.
Endocrinology. 2022 Jan 1;163(1). doi: 10.1210/endocr/bqab138.
Adipose tissue distribution in the human body is highly heterogeneous, and the relative mass of different depots is differentially associated with metabolic disease risk. Distinct functions of adipose depots are mediated by their content of specialized adipocyte subtypes, best exemplified by thermogenic adipocytes found in specific depots. Single-cell transcriptome profiling has been used to define the cellular composition of many tissues and organs, but the large size, buoyancy, and fragility of adipocytes have rendered it challenging to apply these techniques to understand the full complexity of adipocyte subtypes in different depots. Discussed here are strategies that have been recently developed for investigating adipocyte heterogeneity, including single-cell RNA-sequencing profiling of the stromal vascular fraction to identify diverse adipocyte progenitors, and single-nuclei profiling to characterize mature adipocytes. These efforts are yielding a more complete characterization of adipocyte subtypes in different depots, insights into the mechanisms of their development, and perturbations associated with different physiological states such as obesity. A better understanding of the adipocyte subtypes that compose different depots will help explain metabolic disease phenotypes associated with adipose tissue distribution and suggest new strategies for improving metabolic health.
人体内脂肪组织的分布具有高度异质性,不同部位的相对质量与代谢性疾病风险差异相关。脂肪组织的不同功能是由其特化脂肪细胞亚型的含量介导的,这在特定部位的产热脂肪细胞中得到了最好的例证。单细胞转录组谱分析已被用于定义许多组织和器官的细胞组成,但由于脂肪细胞体积大、浮力大和脆弱,使得这些技术难以应用于了解不同部位脂肪细胞亚型的全部复杂性。本文讨论了最近开发的用于研究脂肪细胞异质性的策略,包括对基质血管部分进行单细胞 RNA 测序分析以鉴定不同的脂肪细胞祖细胞,以及单细胞测序分析以描述成熟脂肪细胞。这些努力正在对不同部位的脂肪细胞亚型进行更全面的描述,深入了解其发育机制,并揭示与肥胖等不同生理状态相关的扰动。更好地理解构成不同部位的脂肪细胞亚型将有助于解释与脂肪组织分布相关的代谢性疾病表型,并为改善代谢健康提供新的策略。