Genetic and epigenetic control of adipose development

Abstract

White adipose tissue (WAT) is the primary energy storage organ and its excess contributes to obesity, while brown adipose tissue (BAT) and inducible thermogenic (beige/brite) adipocytes in WAT dissipate energy via Ucp1 to maintain body temperature. BAT and subcutaneous WAT develop perinatally while visceral WAT forms after birth from precursors expressing distinct markers, such as Myf5, Pref-1, Wt1, and Prx1, depending on the anatomical location. In addition to the embryonic adipose precursors, a pool of endothelial cells or mural cells expressing Pparγ, Pdgfrβ, Sma and Zfp423 may become adipocytes during WAT expansion in adults. Several markers, such as Cd29, Cd34, Sca1, Cd24, Pdgfrα and Pref-1 are detected in adult WAT SVF cells that can be differentiated into adipocytes. However, potential heterogeneity and differences in developmental stage of these cells are not clear. Beige cells form in a depot- and condition-specific manner by de novo differentiation of precursors or by transdifferentiation. Thermogenic gene activation in brown and beige adipocytes relies on common transcriptional machinery that includes Prdm16, Zfp516, Pgc1α and Ebf2. Moreover, through changing the chromatin landscape, histone methyltransferases, such as Mll3/4 and Ehmt1, as well as demethylases, such as Lsd1, play an important role in regulating the thermogenic gene program. With the presence of BAT and beige/brite cells in human adults, increasing thermogenic activity of BAT and BAT-like tissues may help promote energy expenditure to combat obesity.

Adipokines: A gear shift in puberty

“…BAT consists of adipocytes containing multiple lipid droplets and mitochondria and plays a role in thermogenesis. Adipocytes in WAT contain only a few mitochondria and a single lipid droplet . Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines (hormones, cytokines, and peptides) .…”

“…Adipocytes in WAT contain only a few mitochondria and a single lipid droplet . Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines (hormones, cytokines, and peptides) . Adipokines are involved in a number of physiological processes including blood pressure, metabolism, glucose, and vascular homeostasis and may play amongst others a key role in puberty onset …”

Role of small proliferative adipocytes: possible beige cell progenitors

“…A recent study identified PRX1 as a marker of s.c. adipose progenitor (Krueger et al 2014, Sanchez-Gurmaches et al 2015. On the other hand, PDGFRα, PDGFRβ, and DLK1 are expressed in both adipose progenitors (Hudak et al 2014, Lee et al 2015, Vishvanath et al 2015, Gulyaeva et al 2018. In the same way, PLF is considered as a common marker of SPA in s.c. and visceral fat.…”

3,5 Diiodo-l-Thyronine (T2) Promotes the Browning of White Adipose Tissue in High-Fat Diet-Induced Overweight Male Rats Housed at Thermoneutrality

“…Brite or beige adipocytes have a white fat-like phenotype, but acquire a brown fat-like phenotype when stimulated by physiological stimuli such as cold [16,17], exercise/dietary [18,19], certain hormones [17,20], or chemical treatments [21], possibly leading to increased thermogenesis [22,23]. This process is referred to as browning and was found to take place primarily in subcutaneous WAT (sWAT) [24,25,26]. The growing interest in brown and beige adipocytes comes from the ability of these cells to exert a significant impact on whole-body metabolism.…”

“…Elucidating the physiology of beige/brite cells and identifying potential molecules or compounds that selectively act on their recruitment are interesting objectives to be achieved. Several studies have suggested that “browning” may be due to two main mechanisms: transdifferentiation of white adipocytes and de novo differentiation of beige/brite adipocytes [26]. Many genes and pathways involved in brown and beige adipocyte biology were suggested, including Prdm16 and certain miRNAs.…”