Determinants of brown adipocyte development and thermogenesis.

ABSTRACT

The brown adipocyte is a thermogenic cell. Its thermogenic potential is conferred by uncoupling protein-1, which 'uncouples' adenosine triphosphate synthesis from energy substrate oxidation. Brown fat cells in so-called classical brown adipose tissue (BAT) share their origin with myogenic factor-5-expressing myoblasts. The development of myocyte/brown adipocyte progenitor cells into a brown adipocyte lineage is apparently triggered by bone morphogenetic protein-7, which stimulates inducers of brown fat cell differentiation, such as PRD1-BF1-RIZ1 homologous domain-containing-16 and peroxisome proliferator-activated receptor-γ co-activator-1-α. The control of brown fat cell development and activity is physiologically ensured by the sympathetic nervous system (SNS), which densely innervates BAT. SNS-mediated thermogenesis is largely governed by hypothalamic and brainstem neurons. With regard to energy balance, the leptin-melanocortin pathway appears to be a major factor in controlling brown adipocyte thermogenesis. The involvement of this homeostatic pathway further supports the role of the brown adipocyte in energy balance regulation. The interest for the brown fat cell and its potential role in energy balance has been further rejuvenated recently by the demonstration that BAT can be present in substantial amounts in humans, in contrast to what has always been thought. Positron emission tomography/computed tomography scanning investigations have indeed revealed the presence in humans of important neck and shoulder cold-activable BAT depots, in particular, in young, lean and female subjects. This short review summarizes recent progress made in the biology of the brown fat cell and focuses on the determinants of the brown adipocyte development and activity.