Emerging Complexities in Adipocyte Origins and Identity

The global incidence of obesity and its comorbidities continues to rise along with a demand for novel therapeutic interventions. Brown adipose tissue (BAT) is attracting attention as a therapeutic target because of its presence in adult humans and high capacity to dissipate energy as heat, and thus burn excess calories, when stimulated. Another potential avenue for therapeutic intervention is to induce, within white adipose tissue (WAT), the formation of brown-like adipocytes called brite (brown-like-in-white) or beige adipocytes. However, understanding how to harness the potential of these thermogenic cells requires a deep understanding of their developmental origins and regulation. Recent cell-labeling and lineage-tracing experiments are beginning to shed light on this emerging area of adipocyte biology. We review here adipocyte development, giving particular attention to thermogenic adipocytes.

TrendsThe developmental origins of adipose tissue and the mechanisms controlling its expansion are only now beginning to be revealed. Although the tools and techniques used to study adipocyte development still need refinement, the emerging picture is that adipocyte development is complex. Brown, brite (or beige), and white adipocytes may have multiple developmental origins.In addition to giving rise to brown adipocytes and skeletal muscle cells, precursor cells expressing the Myf5 promoter also give rise to some white/brite adipocytes.It is currently under debate whether subcutaneous brite/beige adipocytes arise by interconversion or transdifferentiation from particular existing mature adipocytes, or de novo from precursors, and strong evidence supports both models.Whether brown or brite/beige adipocytes are more prevalent in adult humans is also unclear. Emerging data suggest heterogeneity dependent upon multiple factors.