ORF51-06 - Impaired Adaptive Brown Adipose Tissue (BAT) Thermogenesis in Arcuate Kisspeptin-Deficient Female Mice

Kisspeptin (Kiss1) neurons in the arcuate nucleus (ARC), which co-express neurokinin B (NKB/Tac2) and dynorphin to form the KNDy neuronal population, integrate reproductive and metabolic signals. We previously observed that conditional deletion of Kiss1 from Pdyn-expressing ARC neurons reduces energy expenditure, accompanied by altered hypothalamic Tac2 signaling and BAT lipid accumulation with reduced thermogenic gene expression, suggesting impaired adaptive thermogenesis. We hypothesized that ARC Kiss1 signaling is required for adaptive thermogenesis and maintenance of core body temperature (CBT) during thermal challenges. Adult female Pdyn Cre; Kiss1fl/fl (Kiss1 KO), wild type (WT), and ovariectomized (OVX) mice underwent continuous CBT telemetry under thermoneutral (30°C), room temperature (23°C), and cold (4°C) conditions across light and dark phases. Infrared imaging quantified the interscapular BAT to back temperature gradient (ΔT) as an index of thermogenic output. KO mice exhibited impaired thermoregulation compared with WT controls, with effects dependent on environmental temperature and circadian phase. At room temperature, KO mice significantly lowered CBT, exceeding the reductions observed in OVX mice. During cold exposure, both KO and OVX mice failed to maintain CBT, indicating concurrent thermogenic vulnerability to severe cold stress. At thermoneutrality, Kiss1 KO and OVX WT mice exhibited lower CBT similar to that observed under other thermal conditions. Infrared imaging confirmed that the thermoregulatory impairment in KO mice resulted from a reduction in interscapular BAT-to-back temperature gradients (ΔT). These findings demonstrate that ARC Kiss1 signaling is essential for adaptive thermogenesis and the maintenance of thermal stability, positioning KNDy neurons as a central hypothalamic node linking reproductive neuroendocrine pathways to energy homeostasis.