Small proliferative adipocytes: identification of proliferative cells expressing adipocyte markers [Review]

Abstract

It has been thought that adipocytes lack proliferative ability and do not revert to precursor cells. However, numerous findings that challenge this notion have also been reported. The idea that adipocytes dedifferentiate to fibroblast-like cells with increasing cell number was reported in 1975. This possibility has been ignored despite knowledge gained in the 1990s regarding adipocyte differentiation. Several studies on proliferation and dedifferentiation of adipocytes have been published, most of which were conducted from the perspective of regenerative medicine. However, the concept of proliferation of adipocytes remains unclear. In this study, we postulate a new population of adipocytes, which consist of small sized cells (less than 20 μm in diameter) expressing adipocyte markers, such as adiponectin and peroxisome proliferator-activated receptor γ (PPARγ), but not possessing large lipid droplets. These cells show marked ability to incorporate 5-bromo-2'-deoxyuridine (BrdU), for which reason we termed them "small proliferative adipocytes (SPA)". In addition, SPA are observed in the stromal vascular fraction. Since SPA are morphologically different from mature adipocytes, we regarded them as committed progenitor cells. When proliferation of adipocytes in vivo is assessed by measuring BrdU incorporation and expression levels of proliferating cell nuclear antigen (PCNA) in isolated fractions of adipocytes from adipose tissues, subcutaneous SPA proliferate less actively than visceral SPA. Treatment with pioglitazone increases the number of proliferating SPA in subcutaneous, but not visceral, fat, suggesting that SPA may be important in regulating systemic insulin sensitivity and glucose metabolism.

Cell-cycle arrest in mature adipocytes impairs BAT development but not WAT browning, and reduces adaptive thermogenesis in mice

“…Adipocyte numbers in fat tissue can drastically change, depending on the physiological context 3 , 4 . During WAT hyperplasia, mature adipocytes, in addition to preadipocytes, arguably contribute to an increase in cell number, although mature adipocytes are post-mitotic terminally-differentiated cells 21 – 23 . Here using Tg mice with over-expression of p27 in mature adipocytes under the control of the aP2 promoter, we found that the WAT of Tg mice was similar to that of WT mice, both in weight and morphology.…”

“…However, it has been repeatedly suggested that proliferation of mature adipocytes may also be involved in adipose tissue hyperplasia. During WAT hyperplasia, isotope-labeled thymidine was incorporated not only into the preadipocyte fraction, but also, into the mature adipocyte fraction 21 – 23 , although they are possibly attributed to the coexisting of adipose stem cells in this fraction. Primary cultured adipocytes can proliferate even after differentiation 24 , 25 .…”

Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway

“…Our present results showed that under extended hypoxic stress, incorporation of BrdU in human glioma U87-MG cells was repressed in concentration-and time-dependently. BrdU incorporation in cells can be measured to explain cell cycle processing in order to monitor the status of cell proliferation (35). Thus, this study demonstrated the suppressive effects of extended hypoxia on the proliferation of human glioma cells.…”

Role of small proliferative adipocytes: possible beige cell progenitors

“…We previously identified SPA as a novel population of cells expressing both adipocyte-specific genes and proliferative activity in adipose tissue (Kajita et al 2013). In this study, we focused on the characteristics of SPA.…”