Figure 3. Hif2α^ΔGut does not affect the response to VSG surgery.

(A) At termination, Hif2α is effectively knocked down in duodenal mucosal samples from Cre-expressing mice. Average ± SEM; WT-sham, n = 25; WT-VSG, n = 18; Hifα^ΔGut-sham, n = 25; Hifα^ΔGut-VSG, n = 20. Two-way ANOVA: F_{1, 33} = 25.56, ****p < 0.001.

(B) At termination, Cre is expressed in the duodenum of Hif2α^f/fVillin^CreERT (Hifα^ΔGut) mice 84 days after tamoxifen Cre induction independent of surgery. Two-way ANOVA: F_{1, 33} = 105.6, ****p < 0.001. Average Ct data are available in Table S3.

(C) Following VSG, mice follow a similar BW trajectory independent of genotype. rm-ANOVA: F_{51, 1638} = 4.851, ####p < 0.0001 post hoc Tukey test.

(D) Glucose levels following i.p. glucose administration (2 g/kg glucose) are lowered after VSG compared with sham surgery independent of genotype. rm-ANOVA: F_{18, 301} = 1.575, ####p < 0.0001 post hoc Tukey test, multiple comparisons **p < 0.05. The glucose area under the curve is lowered in VSG mice. Two-way ANOVA: F_{1, 43} = 0.2606, ##p < 0.01 surgery effect, *p < 0.05 post hoc Tukey test.

(E) Total GLP-1 response 15 min after oral nutrient exposure (2 g/kg glucose in Ensure Plus) was increased after VSG; two-way ANOVA: F_{1, 84} = 2.619, ####p < 0.0001), but not dependent on genotype.

(F) Food intake is reduced following VSG compared with sham surgery independent of genotype. rm-ANOVA: F_{42, 1250} = 2.826, ####p < 0.0001 post hoc Tukey test.

(G) Hepatic triglyceride levels were lower in Hif2α^ΔGut mice. Average ± SEM; WT-sham, n = 8; WT-VSG, n = 9; Hifα^ΔGut-sham, n = 11; Hifα^ΔGut-VSG, n = 12. Two-way ANOVA: F_{1, 36} = 8.891, **p < 0.01 main effect Hif2α^ΔGut, #p < 0.05 post hoc Tukey test.

(H) No effects of surgery or genotype on hepatic total cholesterol levels were observed.