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Genetic and epigenetic control of adipose development

Gulyaeva, Olga, Dempersmier, Jon, Sul, Hei Sook
Biochimica et biophysica acta 2019 v.1864 no.1 pp. 3-12
adipocytes, adults, body temperature, brown adipose tissue, chromatin, endothelial cells, energy expenditure, epigenetics, gene activation, genes, histones, methyltransferases, obesity, peroxisome proliferator-activated receptor gamma, platelet-derived growth factor receptor alpha, platelet-derived growth factor receptor beta, primary energy, transcription (genetics), white adipose tissue
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.