Tracking adipogenesis during white adipose tissue development, expansion and regeneration

Abstract

White adipose tissue displays high plasticity. We developed a system for the inducible, permanent labeling of mature adipocytes that we called the AdipoChaser mouse. We monitored adipogenesis during development, high-fat diet (HFD) feeding and cold exposure. During cold-induced ‘browning’ of subcutaneous fat, most ‘beige’ adipocytes stem from de novo–differentiated adipocytes. During HFD feeding, epididymal fat initiates adipogenesis after 4 weeks, whereas subcutaneous fat undergoes hypertrophy for a period of up to 12 weeks. Gonadal fat develops postnatally, whereas subcutaneous fat develops between embryonic days 14 and 18. Our results highlight the extensive differences in adipogenic potential in various fat depots.

Surgical injury induces local and distant adipose tissue browning

“…Beige cells that are induced by cold exposure or b3 agonist treatment arise through transdifferentiation 13 of existing white adipocytes or by de novo adipogenesis from a subgroup of precursor cells. 7,11,12 Here, adipose tissue injury resulted in loss of precursor PDGFRa C CD34 C and PDGFRa C Sca1 C cells, suggesting that those precursors are likely not responsible for surgery-induced browning, as suggested by previous reports. 13,14 Surprisingly, surgical trauma not only induces browning locally, but also in the contralateral inguinal and perivascular adipose depots, suggesting that surgical injury triggers systemic pathway(s).…”

“…In addition to clear dying white adipocytes, and recruit new beige adipocytes from progenitors, 7,[10][11][12] alternatively activated macrophages have been implicated in the browning process, acting as an alternative catecholamine source. 16 In the current study, after one day, the injured inguinal depot displayed a 4-fold increase in F4/80 C CD11b C monocytes/macrophages.…”

“…1,[5][6][7] In prevailing models of browning, the central nervous system triggers pathways such as sympathetic discharge, resulting in the release of norepinephrine (NE) and b-adrenergic receptor activation in WAT and BAT. 8 Beige adipocytes arise from both de novo adipogenesis of a subgroup of precursor cells expressing plateletderived growth factor receptor a (PDGFRa), CD34, and Sca-1 7,9,10,11,12 and pre-existing adipocytes (transdifferentiation), 13,14 depending on depot, diet and temperature. During browning, replacement of white adipocytes by de novo generated beige adipocytes is facilitated by alternatively activated macrophages.…”

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

“…In addition to classical brown adipose tissue (BAT) depots, pockets of UCP1‐positive, multilocular adipocytes have also been described within white adipose tissue (WAT) from rodents following cold exposure,2, 3, 4 treatment with a beta 3‐adrenergic agonist,5 or exercise training 6. These adipocytes are commonly referred to as beige, brite (from brown in white), inducible, or recruitable, reviewed in Chechi et al 7 and seem to result from the transdifferentiation of previously unilocular, white adipocytes4, 5 and from the de novo differentiation of precursor cells 8. It has been proposed that beige adipocytes can derive from a distinct precursor and display a gene expression pattern different from that of brown adipocytes 9.…”

Morphogenetics in brown, beige and white fat development

“…26 The origin of beige cells is still a matter of debate, whether they arise from transdifferentiation of white preadipocytes or preexisting mature white adipocytes 2,9 or via de novo differentiation of resident progenitors. 28 Although the source of beige adipocytes is currently debated, the origins of classical brown and white adipocytes are clearer. Lineage tracing studies have established that classical brown adipocytes arise from a Myf5 C skeletal muscle lineage, 18 while adult white adipocytes arise from SMA C mural cells present in the adipose vasculature.…”