Beige adipocytes are defined as Ucp1 + , multilocular adipocytes within white adipose tissue (WAT) that are capable of thermogenesis, the process of heat generation. In both mouse models and humans, the increase of beige adipocyte population, also called WAT browning, is associated with certain metabolic benefits, such as reduced obesity and increased insulin sensitivity. In this review, we summarize the current knowledge regarding WAT browning, with a special focus on the beige adipocyte plasticity, collectively referring to a bidirectional transition between thermogenic active and latent states in response to environmental changes. We further exploit the utility of a unique beige adipocyte ablation system to interrogate anti-obesity effect of beige adipocytes in vivo.It has been well established that activity of beige adipocytes is dominantly regulated by the sympathetic nervous system, induced by the cold or just the feeling of cold ( Figure 1) [6][7][8]. Chemical denervation with 6-hydroxydopamina, prior to 3-week-old age or prior to cold exposure, impairs beige adipocyte formation, indicating the importance of sympathetic nerves during WAT browning [21]. Previous studies on anatomical positioning of sympathetic nerves in the subcutaneous inguinal white adipose tissue (iWAT), for example, by staining the tyrosine hydrolase + (Th + ) sympathetic nerves in fixed tissues [22,23], lack spatial and temporal precision [21,24,25]. Th + -sympathetic nerves and beige adipocytes are not distributed evenly across iWAT [22], suggesting that anatomic positioning of sympathetic nerves may also contribute to beige adipocyte formation. However, the actions of sympathetic nerves, the engagement of neurotransmitters, and their receptors at the contact sites of the sympathetic nerve and receiving cell in live mice are most unknown, and functional relevance of sympathetic nerve neurotransmission in beige adipocyte plasticity, especially during the postnatal period, is not fully elucidated yet.Cells 2019, 8, 1552 2 of 16 environment, but their appearances are also negatively correlated with aging and obesity, suggesting a potential role of beige adipocytes in regulating energy homeostasis.
Beige Adipocyte Formation: Different PlayersIt has been well established that activity of beige adipocytes is dominantly regulated by the sympathetic nervous system, induced by the cold or just the feeling of cold (Figure 1) [6][7][8]. Chemical denervation with 6-hydroxydopamina, prior to 3-week-old age or prior to cold exposure, impairs beige adipocyte formation, indicating the importance of sympathetic nerves during WAT browning [21]. Previous studies on anatomical positioning of sympathetic nerves in the subcutaneous inguinal white adipose tissue (iWAT), for example, by staining the tyrosine hydrolase + (Th + ) sympathetic nerves in fixed tissues [22,23], lack spatial and temporal precision [21,24,25]. Th + -sympathetic nerves and beige adipocytes are not distributed evenly across iWAT [22], suggesting that anatomic positioning of sympatheti...