Fig. 6

Liver ERα/β in F1 females is required for the glucose phenotypes of paternal iAs. (a) Experimental scheme for adult-onset liver-specific knockout of ERα/β in mice carrying double floxed ERα/β alleles through AAV injection at 19 weeks old. (b) RT-qPCR analysis of ERα/β in the liver of F1 females injected with AAV expressing GFP or Cre, n = 8 mice. (c) Western blot analysis of ERα and ERβ in the liver of F1 females injected with AAV-GFP or AAV-Cre, n = 4 mice. (d-e) Glucose tolerance test (GTT) and area under the curve (AUC) in F1 females (F1-F) at 27 weeks old, n = 8–12 mice per group. (f-g) Insulin tolerance test (ITT) in F1 females at 33 weeks old, n = 8–9 mice. (h-i) Pyruvate tolerance test (PTT) in F1 females at 31 weeks old, n = 8–9 mice. (j-k) RT-qPCR analysis of gluconeogenic genes in the liver of F1 females under fasting or refed condition. The mean value in the con-GFP or con-Cre groups was set as 1. n = 4–5 mice. (l-m) Glucose output (GOP) assay in primary hepatocytes from F1 females at 30 weeks old injected with AAV-GFP or AAV-Cre, n = 3 mice. Two-way ANOVA with the Holm-Sidak method was used to analyze GTT, PTT, ITT, gene expression levels, and GOP. Two-sided t-test was used to analyze 2-group AUC of kinetic metabolic tests. Data are mean ± S.E.M. * P < 0.05 between conF1 and iAsF1 groups under the same conditions