title: Leptin amplifies the action of thyrotropin-releasing hormone in the solitary nucleus: an in vitro calcium imaging study.
abstract: Leptin exerts a powerful permissive influence on neurogenic thermogenesis. During starvation and an absence of leptin, animals cannot produce thermogenic reactions to cold stress. However, thermogenesis is rescued by restoring leptin. We have previously observed a highly cooperative interaction between leptin and thyrotropin-releasing hormone [TRH] to activate hindbrain-generated thermogenic responses (Hermann et al., 2006). In vivo physiological studies (Rogers et al., 2009) suggested that the thermogenic impact of TRH in the hindbrain is amplified by the action of leptin through a leptin receptor-mediated production of phosphoinositol-trisphosphate [PIP3]. In turn, PIP3 can activate a tyrosine kinase whose target is the Src-SH2 regulatory site on the phospholipase C [PLC] complex. The TRH receptor signals through the PLC complex. Our immunohistochemical studies (Barnes et al., 2010) suggest that this transduction interaction between leptin and TRH occurs within neurons of the solitary nucleus [NST], though this interaction had not been verified. The present in vitro live cell calcium imaging study shows that while medial NST neurons are rarely activated by leptin alone, leptin pre-treatment significantly augments NST neurons' responsiveness to TRH. This leptin-mediated priming of NST neurons was uncoupled by pre-treatment with the phosphoinositide 3-kinase [PI3K] inhibitor [wortmannin], the phospholipase C inhibitor [U73122] and the Src-SH2 antagonist [PP2]. TTX did not eliminate the synergistic response of the agonists, thus the sensitization cannot be attributed to pre-synaptic mechanisms. It seems likely that NST neurons are involved in the leptin-mediated increase in BAT temperature by sensitizing the TRH-PLC-IP3-calcium release mechanism.
authors.affiliation: Laboratory of Autonomic Neurosciences, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Rogers
authors.forename: David H
authors.initials: DH
authors.lastname: McDougal
authors.forename: Gerlinda E
authors.initials: GE
authors.lastname: Hermann
mesh_terms: D002001:Adipose Tissue, Brown / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005456:Fluorescent Dyes; D020738:Leptin / Q000502:physiology*; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D012249:Rhombencephalon / Q000737:chemistry / Q000378:metabolism; D017552:Solitary Nucleus / Q000737:chemistry* / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism* / Q000502:physiology
chemical_list: D005456:Fluorescent Dyes; D020738:Leptin; D013973:Thyrotropin-Releasing Hormone; D002118:Calcium