Understanding thermoregulation within the range of low body temperatures (Tb) in homeotherms is of special interest in various life science fields. Here, we report that mice exhibit long-lasting hypothermia induced by the administration of an A1 adenosine receptor (A1AR) agonist, N6-cyclohexyladenosine (CHA), in combination with pretreatment with bezafibrates (BZ), a peroxisome proliferator-activated receptor α (PPARα) agonist. Before the induction of hypothermia by CHA administration at a dose of 0.5 mg/kg, CBA/N mice were fed 0.5% BZ-supplemented food for 10 days at an ambient temperature of 23-24℃. Ten days after BZ treatment, intraperitoneal CHA administration induced low Tb (1AR, thereby prolonging low Tb. Both receptors are considered key factors in controlling torpor and/or hibernation; however, a synergistic relationship between these receptors has not been reported. Therefore, our findings suggest that metabolic activation of lipid catabolism via PPARα signaling may potentiate the hypothermic effects induced by A1AR activation.
Sato-Hashimoto et al. (2026) studied this question.