Fifty shades of white: Understanding heterogeneity in white adipose stem cells

The excessive expansion of white adipose tissue underlies the global obesity epidemic. However, not all fat is equal, and the impact of heterogeneity on the development and expansion of different adipose depots is becoming increasingly apparent. Two mechanisms are responsible for the growth of adipose tissue: hyperplasia (increasing adipocyte number) and hypertrophy (increasing adipocyte size). The former relies on the differentiation of adipocyte stem cells, which reside within the adipose stromal vascular fraction. Many differences in gene expression, adipogenesis, and the response to obesogenic stimuli have been described when comparing adipose stem cells from different depots. Considering that there is disparity in the pathogenicity of the depots, understanding this heterogeneity has clinically relevant implications. Here we review the current knowledge surrounding such differences, in the context of development, expansion and therapeutics. Moreover, given the importance of these differences, we suggest that careful consideration for the precise methodologies used, is essential if we are to truly understand the physiologically relevant consequences of this heterogeneity.