Fig. 3: P57 mainly targets PDXK in hypothalamus to induces hypothermia.

a LC-MS detection of PL in hypothalamus (left) and brain tissues (right). Hypothalamus and brain tissue were sampled at 0 min, 30 min and 90 min after treated with P57 (25.0 mg/kg), n = 12 mice, student’s t test. b Schematic showing the bilateral injection of drug into the POA. Coronal brain sections showing location of cannula implanted in POA. Scale bars, 2 mm. c Rectal temperature of mice treated with P57 in the POA. 15 mg/mL or 30 mg/mL P57 (0.6 mg/kg or 1.2 mg/kg,) was injected into POA bilaterally at 0 min (arrow) (400 nL for each laterally). n = 3 mice, two-way ANOVA. d Schematic showing the bilateral injection of virus into the POA. Coronal brain sections showing EGFP (upper right) or Cre-EGFP (lower right) expressed in POA. Scale bars, 500 μm. e, f Core temperature of P57-treated mice with conditional knockout PDXK or not in POA. Virus were injected into hypothalamus bilaterally and let the mice recover for one month, then P57 (25 mg/kg) was injected intraperitoneally, n = 3 mice, two-way ANOVA. g Core temperature of mice with conditional knockout PDXK or not in POA. Mice were treated with cold exposure (10 °C) for 24 h, n = 3 mice. h Core temperature of PL-treated mice. PL was injected intraperitoneally, n = 6 mice, two-way ANOVA. i Core temperature of mice treated with PL in the POA. 100 mg/mL or 200 mg/mL PL (5.0 mg/kg or 10.0 mg/kg) was injected into POA bilaterally (500 nL for each laterally), n = 4 mice, student’s t test. j Core temperature of mice treated with combination of PL (200.0 mg/kg) and P57 (12.5 mg/kg). PL or P57 was injected intraperitoneally into C57BL/6 J male mice, n = 5 mice, two-way ANOVA. Student’s t test used was two-sided. All error bars are presented as mean values  ±  s.e.m. * P < 0.05, ** P < 0.01, *** P < 0.001 and ns, not significant. Source data are provided as a Source Data file.