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III. Characteristics and Ontogeny

A. Tissue characteristics

White adipocytes are typified by their round appearance, containing a large single lipid droplet, displacing the nucleus to the periphery. Morphologically, brown adipocytes differ from white adipocytes by their polygonal shape, smaller size, central nucleus, and numerous small lipid droplets, lending them a multilocular appearance. Brown adipocytes contain well-developed mitochondria filling most of the cytoplasm. The high density of mitochondria is comparable to that of cardiomyocytes. In contrast, the mitochondrial content of white adipocytes is low. BAT is also endowed with a rich blood and nerve supply and a dense niche of perivascular mesenchymal cells, which are a nursery of preadipocytes. The abundance of mitochondria containing respiratory chain cytochrome enzymes with iron as a cofactor, as well as the vasculature within BAT, gives rise to a darker red (brown) color, compared with the paler hue exhibited by WAT.


B. Ontogeny

Because both WAT and BAT accumulate lipid droplets, the traditional view is that they share a common developmental origin. Recent evidence has revealed the existence of brown adipocyte-like cells within WAT, which harbor transcriptional regulators for differentiation into brown adipocytes. This section will outline common factors determining brown and white adipogenesis and developmental differences between BAT and WAT. The implications of these findings in human BAT are explored.

1. Transcriptional control of adipogenesis

Information on the developmental origin of BAT is drawn from rodent studies. BAT and WAT originate from mesenchymal stem cells, which can differentiate into adipocytes, osteoblasts, chondrocytes, and myoblasts (35). Adipogenesis comprises the 2 stages of commitment and differentiation. With appropriate stimulation, mesenchymal stem cells undergo a process of commitment in which they are recruited to an adipocyte lineage (preadipocytes), subject to clonal expansion, followed by terminal differentiation into mature adipocytes.

Brown and white adipocyte differentiation begins with commitment to adipogenesis, a process culminating in the accumulation of intracellular lipid. Adipogenesis is controlled by a cascade of interactions between several transcription factors, chiefly the CCAAT/enhancer-binding proteins (C/EBPs) α, β, and δ; peroxisome proliferator-activated receptor γ (PPAR-γ); and steroid response element-binding protein 1c (SREBP1c) (36, 37) (Figure 1).



Figure 1. Origins and gene expression signatures of white, beige/brite, and brown adipocytes. Mesenchymal stem cells are multipotent, giving rise to the precursors of different adipocyte populations in addition to chondrocytes, osteoblasts, and myocytes. In these precursor cells, those expressing Myf5, originally thought to be a myogenic marker, can be differentiated to produce either brown adipocytes or myocytes (58). The transcriptional regulator PRDM16 controls the fate of these cells. Alternatively, a pool of Myf5-negative precursor cells can be induced to form white adipocytes as well as a recently identified population of beige/brite adipocytes in depots of white adipose tissue (84). Beige adipocyte precursors can be separated from other (white) preadipocytes by sorting using the markers CD137 or TMEM26 (97). Terminal differentiation in all 3 types of adipocytes is controlled 

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