Fig. 6: Inhibition of V-ATPase abrogates HFD-induced weight gain which is dependent on the adipocyte expression of Atp6v0a1.

a Average daily food intake (F = 10.21, df = 3, p < 0.001), (WT-VEH n = 7, WT-BFM n = 7, KO- VEH n = 6, KO-BFM n = 6). b weight gain in WT (solid bars) and KO (open bars) mice after 7 days treated with BFM (black) or VEH (red) and fed HFD (F = 3.27, df = 3, p = 0.03), (WT-VEH n = 7, WT-BFM n = 7, KO-VEH n = 6, KO-BFM n = 6). c, d GTT after 3 days of treatment (group: F = 1.19, df = 3, p = 0.33; time: F = 206, df = 4, p < 0.001; genotype X time: F = 4.48, df = 12, p < 0.001), (WT-VEH n = 8, WT-BFM n = 8, KO-VEH n = 7, KO-BFM n = 8), e, f Glucose stimulated insulin secretion, (group: F = 0.35, df = 3, p = 0.78; time: F = 38.62, df = 1, p < 0.001; genotype X time: F = 1.46, df = 3, p = 0.25), (WT-VEH n = 8, WT-BFM n = 8, KO-VEH n = 7, KO-BFM n = 8). g, h ITT after 7 days treatment with BFM (WT-VEH n = 8, WT-BFM n = 7, KO-VEH n = 8, KO-BFM n = 7: F = 8.02, df = 3, p = 0.006; time: F = 74.23, df = 5, p < 0.001; genotype X time: F = 4.25, df = 15, p < 0.001). Relative gene expression in i. hypothalamus (n = 6/group; Agrp: t = 2.506, df = 10, p = 0.03; Npy: t = 0.17, df = 10, p = 0.86; Pomc: t = 4.055, df = 10, p = 0.002; Cart: t = 0.45, df = 10, p = 0.66) and j WAT (n = 7/group; Adipoq: t = 1.71, df = 12, p = 0.11; Lep: t = 1.39, df = 12, p = 0.19; Acaca: t = 0.41, df = 12, p = 0.69; Gdf15: t = 4.33, df = 12, p = 0.001) in vehicle or BFM-treated WT mice after 2 weeks of treatment. Data is expressed as mean ± SEM. a, b were analyzed by one-way ANOVA followed by two-stage linear step-up procedure of Benjamini, Krieger and Yekutieli with false discovery rate of 0.10. c–h were analyzed by repeated-measures two-way ANOVA followed by two-stage linear step-up procedure of Benjamini, Krieger and Yekutieli with false discovery rate of 0.10. i, j were analyzed by student t-test (2 tailed), * denotes statistical significance at p < 0.05.