Figure 8.
Schematic pathway of non-shivering heat thermogenesis in BAT and putative thermoregulation of PACAP under normal and heat conditions. (a) Schematic nerve pathway for non-shivering thermoregulation with BAT. Non-shivering thermogenesis is regulated by the sympathetic nerve innervation. Preganglionic sympathetic nerves from the DMH and RPa project to postganglionic nerves, which innervate into the BAT. The nerves release noradrenaline (NA) and enhance a key thermogenetic molecule, UCP1, mediated by β3-adrenaline receptor (b3AR) and hormone-sensitive lipase (HSL) in the BAT. (b) Putative thermoregulation of the wild-type and PACAP KO mice under normal and heat conditions. The NA contents in the BAT were lower in PACAP KO mice than wild-type mice [24,45]. To compensate for their lower NA contents, the PACAP KO mice exhibited increased expression of b3AR and HSL, therefore, maintaining the UCP1 level and core body temperature. Simultaneously, heat exposure increased PACAP in the POA to inhibit the DMH and RPa nerve signals and decreased the expression of b3AR and HSL to suppress thermogenesis. On the other hand, because of the POA signaling, and because downregulation of b3AR and HSL was involved in the same pathway, the thermoregulation was less effective. However, in PACAP KO mice, thermogenesis depends highly on b3AR and HSL in normal conditions. Therefore, strong suppression of b3AR and HSL expression might result in the suppression of UCP1 and thermogenesis.