Adipose Sensory Nerves: Functional and Neuroanatomical Evidence for Their Emerging Role in Energy Balance

White adipose tissue (WAT) lipolysis is initiated via direct sympathetic nervous system (SNS) innervation and activation. SNS control to WAT is vital to maintaining homeostasis in response to metabolic challenges such as food deprivation and cold exposure. Using transneuronal viral tract tracers, we have identified sensory nerves from WAT that project to brainstem and forebrain areas critical to metabolic function. In addition, these sensory circuits from fat communicate with SNS outflow neurons that project back to fat?forming neural feedback loops throughout the CNS?providing neuroanatomical evidence for sensory WAT-SNS crosstalk. It is unclear, however, what role these WAT-specific sensory nerves serve to inform the CNS of acute and dynamic metabolic challenges to which it can then respond. Here we tested mechanisms of activation of WAT sensory nerves and present a working model to deepen our understanding of why these neural circuits act as conduits for acute metabolic feedback signals from WAT. Neurochemical, neuroanatomical, and neurophysiological evidence supports the presence of: 1) WAT lipolytic sensors from a neural population known to be capable of controlling SNS outflow; and 2) functional neural links among fat depots mediated via the peripheral and central nervous systems.