Figure 2. Development and cyclic remodelling of dWAT.

(a) In mice, the initial development of hair follicles and dWAT, which occurs between embryonic days (E) 12.5 to E16.5, are largely independent from one another^41,42. Reticular progenitor cells and adipose progenitor cells arise from common fibroblast progenitors. Hair follicles develop at the interaction sites between embryonic epidermis and papillary fibroblast progenitor cells. (b) During E17.5 to E18.5, development of hair follicles and dWAT are coupled^{4,41,44,45,110}. Enlarged hair follicles activate several pro-adipogenic signalling pathways, including Hedgehog⁴⁵ and Bmp⁴⁸. In response to hair follicle-derived signals, adipose progenitors rapidly differentiate. Small multilocular adipocytes appear first and then mature into large unilocular cells over several days. (c) dWAT peaks in thickness by postnatal day (P) 12, which is when anagen hair follicles fully develop⁴. dWAT contains differentiated adipocytes and adipocyte progenitor cells. (d, e) Between P19 to 21, hair follicles undergo regression into telogen stage. Concomitantly, dWAT collapses, partially through cell lipolysis to less than half of its anagen size^4,41. At the same time, adipose stem cells (ASCs) expand via proliferation and give rise to late stage adipose progenitor cells (green)⁶. Autocrine Pdgfα mediates the expansion of adipose progenitor cells⁴⁶. (f) During second anagen, up to 40% of adipocytes in enlarged dWAT are new, derived from expanded progenitors⁴⁵.