Neurons in the Ventral Lateral Preoptic (vLPO) Area Inhibit Brown Adipose Tissue (BAT) Thermogenesis

Abstract

Neurons in the preoptic area of the hypothalamus play important roles in thermoregulation. However, the subregions of the preoptic hypothalamus are heterogeneous, such that neuronal activation at some sites elicits hyperthermia, while others evoke hypothermia. Here we show that in urethane/chloralose‐anesthetized, artificially‐ventilated rats, neurons in the vLPO (0.0 to −1.44 mm caudal to bregma, 0.8 to 1.5 mm lateral to the midline, and −8.0 to 9.8 mm below the dura surface, incisor bar in flat skull position) have a hypothermic effect mediated by inhibition of sympathetic nerve activity (SNA) and BAT thermogenesis. The activation of cvLPO neurons with nanoinjections of NMDA (0.2 mM, 60 nl) evoked a complete inhibition of cold‐evoked BAT thermogenesis: BAT SNA (−97 %, p = 0.01), BAT temperature (TBAT, −0.4 °C, p = 0.01), expired CO2, (Exp CO2, −0.4 %, p = 0.0004), mean arterial pressure (MAP, −9 mmHg, p = 0.01) and heart rate (HR, −53 bpm, p = 0.0005). Similar BAT sympathoinhibitory responses were obtained with nanoinjections of bicuculline (BIC, 1.0 mM, 60 nl) in the vLPO. Under thermoneutral conditions, the inhibition of cvLPO neurons by activation of local GABAA receptors (muscimol, 1.2 mM, 60 nl) increased BAT SNA (+99 % p = 0.0001), TBAT (+2.2 °C, p = 0.0001), Exp CO2 (+1.0 %, p = 0.00003), and HR (+58 bpm, p = 0.007), with no change in MAP (p = 0.5). Nanoinjections of muscimol, or the glutamate receptor antagonists, AP5/CNQX, in the dorsomedial hypothalamus (DMH), or in the rostral raphe pallidus (rRPa), reversed the activation of BAT thermogenesis evoked by inhibition of vLPO neurons. Activation of neurons in vLPO inhibited the BAT thermogenesis evoked by BIC nanoinjections in the DMH, but not the increase in BAT SNA evoked by BIC nanoinjections in the rRPa. We conclude that vLPO contains BAT sympathoinhibitory neurons that mediate the warm ambient‐evoked inhibition of BAT thermogenesis through a direct or indirect GABAergic input to rRPa. Similarly to the cold‐evoked activation of BAT thermogenesis, that following inhibition of vLPO neurons requires the glutamatergic, BAT sympathoexcitatory pathway from DMH to BAT sympathetic premotor neurons in rRPa. These novel findings a key population of BAT sympathoinhibitory neurons in the central pathway mediating the skin warming‐evoked inhibition of BAT thermogenesis, requiring the addition of a BAT sympathoinhibitory pathway between vLPO and rRPa to the current model of central autonomic thermoregulation.Support or Funding InformationThis work was supported by NIH R01‐NS091066 (S.F.M.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.