title: Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis.
abstract: OBJECTIVE
  Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve fibers that network to metabolic brain areas; moreover, activation of these afferents is reported to increase sympathetic nervous system outflow. However, the endogenous stimuli sufficient to drive WAT afferents during metabolic challenges as well as their functional relation to BAT thermogenesis remain unknown.
  
  
  METHODS
  We tested if local WAT lipolysis directly activates WAT afferent nerves, and then assessed whether this WAT sensory signal affected BAT thermogenesis in Siberian hamsters (Phodopus sungorus).
  
  
  RESULTS
  2-deoxyglucose, a sympathetic nervous system stimulant, caused β-adrenergic receptor dependent increases in inguinal WAT (IWAT) afferent neurophysiological activity. In addition, direct IWAT injections of the β3-AR agonist CL316,243 dose-dependently increased: 1) phosphorylation of IWAT hormone sensitive lipase, an indicator of SNS-stimulated lipolysis, 2) expression of the neuronal activation marker c-Fos in dorsal root ganglion neurons receiving sensory input from IWAT, and 3) IWAT afferent neurophysiological activity, an increase blocked by antilipolytic agent 3,5-dimethylpyrazole. Finally, we demonstrated that IWAT afferent activation by lipolysis triggers interscapular BAT thermogenesis through a neural link between these two tissues.
  
  
  CONCLUSIONS
  These data suggest IWAT lipolysis activates local IWAT afferents triggering a neural circuit from WAT to BAT that acutely induces BAT thermogenesis.
authors.affiliation: Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA; Center for Obesity Reversal, Georgia State University, Atlanta, GA 30303, USA. Electronic address: johnny.garretson@gmail.com.
authors.forename: John T
authors.initials: JT
authors.lastname: Garretson
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Szymanski
authors.affiliation: Department of Medicine and Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schwartz
authors.affiliation: Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA; Department of Biology, Georgia State University, Atlanta, GA 30303, USA; Center for Obesity Reversal, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Bingzhong
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA 30303, USA; Center for Obesity Reversal, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Ryu
authors.affiliation: Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA; Department of Biology, Georgia State University, Atlanta, GA 30303, USA; Center for Obesity Reversal, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bartness
keywords: Adipose innervation; BAT thermogenesis; Denervation; Lipolysis; WAT sensory