Ventral Lateral Preoptic (vLPO) Neurons Inhibit Brown Adipose Tissue Thermogenesis during Warming of the Preoptic Area

Abstract

Brown adipose tissue (BAT) and shivering thermogenesis and cutaneous vasoconstriction are inhibited in warm climatic conditions to reduce heat production and increase heat dissipation, thereby maintaining core body temperature homeostasis. We tested the hypothesis that the hypothalamic preoptic area (POA) contains warm sensitive neurons (WSNs) that are activated by local warming to produce inhibition of BAT activity. In urethane/α‐chloralose‐anesthetized, artificially‐ventilated rats, warming the POA bilaterally with a thermode (two silver rods connected to a peltier device) increased POA temperature from 35 to 40°C and promptly inhibited skin cooling (35–36°C)‐evoked BAT sympathetic nerve activity (SNA) (from 1061±2.7 to 102±0.1 that corresponds to 100% reduction, p<0.001) and reduced BAT temperature (1.7±0.2, p<0.001), core temperature (0.3±0.1, p<0.05), expired CO2 (0.7±0.1%, p<0.001), heart rate (61±10, p<0.001) and mean arterial pressure (14±6, p<0.05). Bilateral nanoinjections of the GABAA‐agonist, muscimol (500 mM, 100 nl), into the ventral lateral preoptic area (vLPO) prevented (p<0.001) the local POA warming‐induced inhibition of BAT SNA and the reductions in BAT and core temperatures. Blockade of ionotropic glutamate receptors in vLPO with nanoinjections of AP5/CNQX also prevented (p<0.001) the local POA warming‐induced inhibitions of BAT thermogenesis. POA warming failed (p>0.05) to inhibit the elevated BAT SNA following blockade of local GABAA receptors with nanoinjections of bicuculline (BIC) in the rostral raphe pallidus (rRPa), but still effectively inhibited the elevated BAT SNA following BIC nanoinjections in the dorsomedial hypothalamus (DMH). Our results demonstrate that the POA warming‐evoked inhibition of BAT thermogenesis requires activation of GABAA receptors in rRPa, but not those in DMH. In addition, the finding that glutamate receptor blockade in vLPO prevents the POA warming‐induced inhibition of BAT activity, is consistent with WSNs glutamatergically exciting BAT sympathoinhibitory neurons in vLPO to produce the POA warming‐induced inhibition of BAT thermogenesis. These novel findings elucidate the central pathway mediating POA warming‐evoked inhibition of BAT thermogenesis and require the addition of a BAT sympathoinhibitory pathway between vLPO and rRPa to the current model of central autonomic thermoregulation.Support or Funding InformationSupported by NIH R01091066 (SFM).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.