Developmental and functional heterogeneity of white adipocytes within a single fat depot

Recent studies suggest that, even within a single adipose depot, there may be distinct subpopulations of adipocytes. To investigate this cellular heterogeneity, we have developed multiple conditionally immortalized clonal preadipocyte lines from white adipose tissue of mice. Analysis of these clones reveals at least three white adipocyte subpopulations. These subpopulations have differences in metabolism and differentially respond to inflammatory cytokines, insulin, and growth hormones. These also have distinct gene expression profiles and can be tracked by differential expression of three marker genes: Wilms’ tumor 1, transgelin, and myxovirus 1. Lineage tracing analysis with dual‐fluorescent reporter mice indicates that these adipocyte subpopulations have differences in gene expression and metabolism that mirror those observed in the clonal cell lines. Furthermore, preadipocytes and adipocytes from these subpopulations differ in their abundance in different fat depots. Thus, white adipose tissue, even in a single depot, is comprised of distinct subpopulations of white adipocytes with different physiological phenotypes. These differences in adipocyte composition may contribute to the differences in metabolic behavior and physiology of different fat depots. Synopsis While differences between white, beige and brown adipose tissues are relatively well studied, heterogeneity within white adipocytes remains unclear. Here, combined profiling and lineage tracing analyses identify distinct subpopulations of white fat cells even in a single pad, possibly explaining discrepant metabolic behavior and physiology of different depots. Immortalized mouse preadipocyte cell lines display three white adipocyte subpopulations with differential gene expression and markers. Adipocyte subpopulations differ in energy metabolism and response to inflammatory cytokines, insulin, and growth hormones. The adipocyte subpopulations can be distinguished by expression of Wilms’ tumor 1, transgelin, and myxovirus 1. Preadipocytes and adipocytes from these subpopulations show varying abundance in different fat depots in vivo . Graphical Abstract Gene expression profiling and lineage tracing reveal that white fat tissue in mouse is comprised of multiple adipocyte subtypes with distinct metabolic profiles.