Depletion of Iqgap2 blunts hepatic lipid metabolism genes in female mice.Iqgap2−/− and wildtype mice (male and female, 16–20 weeks old, n = 5–9) were fed regular chow ad libitum or fasted for 24 h. Liver tissues were analyzed with qRT-PCR to quantify the mRNA of key genes involved in lipid metabolism. A and F, lipogenic transcription factor Srebp1c was downregulated in both female and male Iqgap2−/− mice. B–C, G –H, however, exhibit sex differences, (B) Fasn and (C) Dgat2 were reduced in female but not in Iqgap2−/− male mice (G and H). Hepatic triglyceride levels were decreased in Iqgap2−/− female (E) but not male mice (J). D, fasting-mediated increases in the expression of Cpt1a gene, crucial in fatty acid oxidation, was diminished in female Iqgap2−/− mice. In contrast, male mice showed significant upregulation of Cpt1a upon fasting (I). Statistics were calculated using two-way ANOVA with Bonferroni post hoc analysis. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001. Fasn, fatty acid synthase; 3; IQGAP2, IQ motif-containing GTPase activating protein 2; Iqgap2−/−, IQGAP2 knockout; Srebp1c, sterol response element binding protein 1c.