Adipose tissue stem cells meet preadipocyte commitment: going back to the future

Abstract

with ill health. Such stigmatization distracts from a fascinating aspect of WAT biology: its enormous plasticity as an organ. Indeed, WAT is capable of massive expansion and contraction in response to chronic alterations in energy balance, accounting for as little as 5% body mass in extremely lean athletes ( 1 ) or as much as 60% body mass in morbidly obese individuals ( 2 ). Moreover in rodents, rabbits, and humans, WAT can regenerate following lipectomy ( 3-6 ). This striking degree of plasticity is unique among organs in adults. On a cellular level, WAT expansion is driven by both hypertrophy and hyperplasia of adipocytes ( 7-13 ). Even in nonexpanding WAT, adipocytes renew frequently to compensate for adipocyte death, with approximately 10% of adipocytes renewed annually ( 14,15 ). These data, which indicate that committed adipocyte progenitors (preadipocytes) exist within WAT, are the product of decades of research motivated largely by our desire to understand adipose tissue in the context of obesity and related diseases. Preadipocytes exist in adipose tissueThough the notion of obesity as a disease has existed since at least the time of Hippocrates ( 16 ), investigation into the origins of the adipocyte and the individual contributions of adipocyte hypertrophy and hyperplasia to adipose bulk began in earnest only after the appearance of the stem cell concept, as related to blood cells, in the early 1900s ( 17 ). In the 1940s, histologic observations of the appearance of adipocytes in chambers implanted in the ears of live rabbits suggested that de novo fat formation was Abstract White adipose tissue (WAT) is perhaps the most plastic organ in the body, capable of regeneration following surgical removal and massive expansion or contraction in response to altered energy balance. Research conducted for over 70 years has investigated adipose tissue plasticity on a cellular level, spurred on by the increasing burden that obesity and associated diseases are placing on public health globally. This work has identifi ed committed preadipocytes in the stromal vascular fraction of adipose tissue and led to our current understanding that adipogenesis is important not only for WAT expansion, but also for maintenance of adipocyte numbers under normal metabolic states. At the turn of the millenium, studies investigating preadipocyte differentiation collided with developments in stem cell research, leading to the discovery of multipotent stem cells within WAT. Such adipose tissue-derived stem cells (ASCs) are capable of differentiating into numerous cell types of both mesodermal and nonmesodermal origin, leading to their extensive investigation from a therapeutic and tissue engineering perspective. However, the insights gained through studying ASCs have also contributed to more-recent progress in attempts to better characterize committed preadipocytes in adipose tissue. Thus, ASC research has gone back to its roots, thereby expanding our knowledge of preadipocyte commitment and adipose tissue biology. -Cawthorn, W. P., E. ...

Human cytomegalovirus infection of human adipose-derived stromal/stem cells restricts differentiation along the adipogenic lineage

“…48 Whether or not HCMV infects adipose tissue in vivo has not been documented. Murine, rat and rhesus cytomegaloviruses have all been detected in adipose tissue.…”

The Transcription Factor Paired-Related Homeobox 1 (Prrx1) Inhibits Adipogenesis by Activating Transforming Growth Factor-β (TGFβ) Signaling

“…For example, bone morphogenetic protein-2 (BMP-2) down-regulates expression of Prrx1 in osteoblast precursors, whereas parathyroid hormone-related protein up-regulates Prrx1 in these cells (13). These effects may contribute to the ability of BMP-2 to promote preadipocyte commitment (4,57) or to inhibition of adipogenesis by parathyroid hormone-related protein (58). Thus, future studies should investigate whether Prrx1 acts downstream of these or other adipogenic regulators.…”

“…Adipogenesis is characterized by dynamic changes in gene expression, whereby anti-adipogenic regulators are down-regulated while gene products required for adipogenesis are transiently or terminally induced (5,6). Such positive and negative regulators ultimately stimulate or inhibit, respectively, the expression and/or activity of peroxisome proliferator-activated receptor-␥ (PPAR␥) 4 and CCAAT/enhancer-binding protein-␣ (C/EBP␣). These so-called "master" adipogenic transcription factors activate expression of fatty acid-binding protein 4 (Fabp4), adiponectin (Adipoq) and other genes encoding proteins responsible for mature adipocyte functions.…”

Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology

“…Besides pre-adipocytes which are defined as immature cells already engaged in the Casteilla et al, 2011;Cawthorn et al, 2012). A common characteristic of all stem cells is that they can self-renew (make copies of themselves) and differentiate into various cell types when cultured in defined media (Figure 1).…”