Fig. 6: ERRα^3SA mice develop insulin resistance.

a Blood glucose concentrations (WT, n = 8; 3SA, n = 7), b serum insulin levels of ND-fed ERRα^3SA and WT littermates in the fed (WT, n = 8; 3SA, n = 6, fasted (n = 7 per group), and refer (WT, n = 8; 3SA, n = 6) conditions. (n = 8; 3SA, n = 6; WT fasted, n = 7; 3SA fasted, n = 7; WT Refed, n = 8; 3SA Refed, n = 6), c Quantification of the insulin signaling cascade components from ND-fed WT and ERRα^3SA littermates upon fasting and refeeding (n = 3 per group). See Supplementary Fig. 6c for immunoblot image. d Liver (n = 5 per group) and muscle (n = 6 per group) glycogen levels of ND-fed ERRα^3SA and WT littermates upon refeeding. e Representative PAS staining of ERRα^3SA and WT littermates post 17-week high-fat feeding. Scale bars, 50 μm. See also Supplementary Fig. 6d for quantitation. f Fasting blood glucose concentrations upon a 16-week HFD (n = 8 per group). g, h Concentrations of fed serum TG (g) (WT, n = 7; 3SA, n = 6) and FFA (h) (n = 6 per group) of ERRα^3SA and WT littermates after 17-week high-fat feeding. i Tolerance test of glucose (GTT) and j insulin (ITT) performed after 6-week and 8-week HFD, respectively. Inset graphs show area under the curve (AUC) (n = 6 per group). k Overlap of DEGs identified in ND-fed ERRα^3SA mice with insulin-regulated DEGs (GSE117741⁶²) (p < 0.05, |FC| ≥ 1.20). l Pdk4 mRNA levels (n = 5 per group). m ChIP-qPCR analysis of ERRα binding to Esrra or Pdk4 promoters. n, o mRNA levels of the indicated genes upon a ND (n = 5 per group). p Muscle FFA levels upon refeeding (n = 6 per group). q mRNA levels of genes encoding proteins involved in glucose and fat metabolism in liver from ERRα^3SA and WT littermates fed a HFD for 17 weeks (n = 8 per group). Data are presented as mean ± SEM, *p < 0.05, unpaired two-tailed Student’s t test (a–d, f–j, l, n–q). Source data are provided as a Source Data file.