Plasticity of Epididymal Adipose Tissue in Response to Diet-Induced Obesity at Single-Nucleus Resolution

Adipose tissues display a remarkable ability to adapt to the dietary status. Here, we have applied single-nucleus RNA-seq to map the plasticity of mouse epididymal white adipose tissue at single-nucleus resolution in response to high-fat-diet-induced obesity. The single-nucleus approach allowed us to recover all major cell types and to reveal distinct transcriptional stages along the entire adipogenic trajectory from preadipocyte commitment to mature adipocytes. We demonstrate the existence of different adipocyte subpopulations and show that obesity leads to disappearance of the lipogenic subpopulation and increased abundance of the stressed lipid-scavenging subpopulation. Moreover, obesity is associated with major changes in the abundance and gene expression of other cell populations, including a dramatic increase in lipid-handling genes in macrophages at the expense of macrophage-specific genes. The data provide a powerful resource for future hypothesis-driven investigations of the mechanisms of adipocyte differentiation and adipose tissue plasticity. [Display omitted] •Single-nucleus RNA-seq recovers nuclei of all major cell types in adipose tissues•HFD-induced obesity induces inflammatory gene programs in most adipose cell types•The lipogenic adipocyte subpopulation is lost in HFD-induced obesity•The in vivo trajectory of adipogenesis reveals distinct transcriptional stages Using single-nucleus RNA-seq, Sárvári et al. show that diet-induced obesity leads to major transcriptional changes in all cell types in the epididymal adipose tissue. They show that in vivo adipocyte differentiation is affected by obesity and demonstrate the existence of three adipocyte subpopulations, one of which is lost in obesity.