Fat cells gobbling up norepinephrine?

Abstract

The sympathetic nervous system (SNS) controls key aspects of adipose tissue (AT) function through the release of norepinephrine (NE) and beta adrenergic signaling. Sympathetic tone is determined by NE release but also by the rate of extracellular NE clearance that historically has been believed to occur solely through solute carrier family 6 member 2 (SLC6A2) expressed on sympathetic neurons. Song and colleagues show that adipocytes can also clear NE through organic cation transporter 3 (Oct3). This contributes to our understanding of how adrenergic signaling is controlled in AT and also emphasizes the need to develop better methods to assess adrenergic signaling in vivo.

Fig 1. NE clearance in AT.

NE released from the synaptic synapse can either signal through ARs or be cleared through uptake into either the sympathetic fiber or macrophages through SLC6A2 and then intracellularly either be recycled or degraded by MAO, or it can extracellularly be degraded through COMT. Reduced NE clearance increases AR signaling, in turn regulating key aspects of white AT function, such as lipolysis, thermogenesis, and release of adipokines. Song and colleagues show that Oct3 enables adipocytes to take up and degrade NE, which affects NE signaling. Ablation of Oct3 in adipocytes increases adrenergic signaling and thereby induces lipolysis, thermogenesis, and browning and reduces adiposity. AR, adrenoceptor; cAMP, cyclic adenosine monophosphate; COMT, catechol-O-methyltransferase; IL-6, interleukin-6; MAO, monoamine oxidase; NE, norepinephrine; Oct3, organic cation transporter 3; PKA, protein kinase A; SAM, sympathetic neuron-associated macrophage; SLC6A2, solute carrier family 6 member 2; SNS, sympathetic nervous system; TNF- α, tumor necrosis factor-α; AT, adipose tissue.