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Activating FOXO1 nuclear entry to enhance cold survival in obese pre-diabetic mice. a Confocal images of XPO1, FOXO1 and DAPI staining in obese mice (12-14 mo) pancreatic sections from indicated conditions (n = 5 mice from 5 experiments); KPT-330, XPO1 inhibitor. b Confocal images of FOXO1 and DAPI in obese mice heart, liver and skeletal muscle sections from indicated conditions (n = 5 mice from 5 experiments). c Survival rate of obese mice at indicated conditions; KPT-330, XPO1 inhibitor; DMSO is the solvent control. d Left: from a representative mouse energy expenditure experiment, heat and oxygen consumption (VO2) of obese mice with an intraperitoneal injection of KPT-330 (3 mg/kg) (n = 7) or DMSO (n = 5) prior to 4 °C exposure; right: average heat and VO2 under basal and cold-exposed conditions. e Daily changes of mouse body weight during 4 °C exposure (KPT-330, n = 9; DMSO, n = 5). f Mouse body mass composition following 10-day cold exposure at indicated conditions (KPT-330, n = 8; DMSO, n = 6). g Venn diagram showing the numbers of overlapped DEGs among indicated tissues from obese mice after 6 h of 4 °C exposure; also see Supplementary Data 3. h Enrichment analysis on DEGs upregulated in brown adipose tissues (BAT), epididymal white adipose tissues (eWAT), skeletal muscles and liver at indicated conditions. Data are shown as mean and SEM. Statistics: two-tailed Student’s t test (d−f); P values in (h) were calculated in Metascape. Scale bars: 20 μm (a, b). Source data are provided as a Source Data file.
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