This condition involves the immediate activation of the orthosympathetic system, with the consequent, immediate functional activation of brown adipocytes via the innervation and the neuro-adipocytic junctions described above. In a matter of hours, activated adipocytes exercise their ther-mogenic function by synthesising new mitochondria and UCP1; in the course of a few days new cells develop, giving rise to a new tissue organisation characterised by an increased number of vessels and nerves [59, 60]. In the framework of the new concept of adipose organ, it is easy to understand that the arising of new brown cells involves not only some areas long considered as pure BAT, but the whole organ. It follows that its macroscopic appearance veers towards a brown aspect and that the microscopic features of the different depots progressively turn them into BAT (Fig. 8).
It is important to note that this process does not necessarily entail the arising of brown adipocytes in white depots - since, as mentioned above, brown cells may be present in the various depots (depending on age, strain, etc.; see above) -but rather an increase in their number [61,62],
Transmission electron microscopic (TEM) studies, which are very sensitive in detecting the different stages of cell development (see 'Development'), have shown that the adipose organ of adult mice and rats kept in thermoneutral conditions and fed a normal diet contains neither totally undifferentiated nor scarcely differentiated cells.
By contrast, in cold-exposed animals undiffer-entiated pericytes and brown preadipocytes (i.e. cells with minimal differentiation features that allow their morphological identification as cells committed to differentiate into brown adipocytes) arise both in BAT and in WAT. Preadipocytes may be found in the pericytic and/or perivascular position, suggesting that cold exposure induces the tissue conditions that lead to the arising of brown preadipocytes in all WAT and BAT areas of the organ. Therefore, irrespective of the existence of distinct white and brown cell precursors, their arising in different depots of adult animals clearly depends on microenvironmental tissue conditions. Cold exposure induces an increased activity of noradrenergic parenchymal fibres and simultaneous branching of nerve fibres both in WAT  and in BAT  areas. In turn, this induces an overall increase in noradrenaline tissue concentration followed by the development of brown cells in the various depots of the organ.
In contrast, development of white pre-adipocytes in the various areas appears to be triggered by different stimuli (see 'Positive Energy Balance: Overweight and Obsesity') directed at increasing the energy storage capacity.
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