TY - JOUR
T1 - Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis
AU - Garretson, John T.
AU - Szymanski, Laura A.
AU - Schwartz, Gary J.
AU - Xue, Bingzhong
AU - Ryu, Vitaly
AU - Bartness, Timothy J.
N1 - Publisher Copyright:
© 2016 The Author(s)
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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. Method 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.
AB - 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. Method 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.
KW - Adipose innervation
KW - BAT thermogenesis
KW - Denervation
KW - Lipolysis
KW - WAT sensory
UR - http://www.scopus.com/inward/record.url?scp=84978174471&partnerID=8YFLogxK
U2 - 10.1016/j.molmet.2016.06.013
DO - 10.1016/j.molmet.2016.06.013
M3 - Article
AN - SCOPUS:84978174471
SN - 2212-8778
VL - 5
SP - 626
EP - 634
JO - Molecular Metabolism
JF - Molecular Metabolism
IS - 8
ER -