Fig. 9: Upregulated Vav2 catalytic activity reduces fat content in white adipocytes.

a Evolution of the body weight of mice of indicated genotypes (inset) that were maintained under the indicated diet conditions (inset) from the 8th to the 26th week of age. Data represent the mean ± SEM. *, P = 0.0274; **, P = 0.0047; ***, P = 0.0001 (WT HFD vs. WT CD mice, 10 weeks), P = 0.00002 (Vav2^Onc/Onc HFD vs. WT HFD mice, 12 weeks), P = 0.0001 (Vav2^Onc/Onc HFD vs. WT HFD mice, 14 and 18 weeks), P = 0.00004 (Vav2^Onc/Onc HFD vs. WT HFD mice, 16 weeks), and P < 0.000001 (rest of analyses) relative to the value obtained with the respective control at the same time-point using two-way ANOVA and Holm–Sidak multiple comparison tests. n = 10 (CD) or 15 (HFD) animals per group used in two or three independent experiments. b Representative image of mice at the end of the experiments shown in a. Scale bar, 1 cm. c Weight of the gonadal WAT mass from CD-fed animals of indicated genotypes (inset) and ages (bottom). Data are presented as mean ± SEM. n = 4 (2.5-month-old mice), 19 (4-month-old mice, 14 (6-month-old WT animals), or 15 (6-month-old Vav2^Onc/Onc mice). d Representative images of gonadal WAT sections from CD-fed 6-month-old mice of indicated genotypes (left). Scale bar, 100 μm. n = 5 (WT) and 6 (Vav2^Onc/Onc) mice. e Distribution of the mean diameter of gonadal white adipocytes from CD-fed 4- (left) and 6-month-old (right) mice of indicated genotypes (inset). Data are shown as mean ± SEM. *, P = 0.0190; **, P = 0.0017 (60 μm, left panel), P = 0.0055 (30 μm, right panel), P = 0.0064 (90 μm, right panel), and P = 0.0035 (40 μm, left panel); ***, P = 0.000009 (30 μm, left panel), P = 0.0001 (40 μm, right panel), and P = 0.0003 (50 and 80 μm, right panel) relative to the value obtained with the respective control at the same time-point using two-way ANOVA followed by Fisher’s LSD tests. n = 6 (6-month-old Vav2^Onc/Onc) and 5 (other conditions) animals per experimental group. f Weight of the gonadal WAT mass from 6-month-old mice of indicated genotypes (inset) that were subjected to either CD or HFD (bottom) for 4 months. Data are presented as mean ± SEM. **, P = 0.0013 relative to the value obtained with the respective control using two-way ANOVA and Holm–Sidak multiple comparison tests. n = 9 (CD-fed WT), 10 (CD- and HFD-fed Vav2^Onc/Onc), and 12 (HFD-fed WT) mice. g Representative images of gonadal WAT sections from 6-month-old mice of the indicated genotypes (top) that were subjected to either CD or HFD conditions (left). Scale bar, 100 μm. n = 4 (CD) and 5 (HFD) animals per experimental group. h Distribution of the mean diameter of gonadal white adipocytes from 6-month-old mice of indicated genotypes that were maintained under CD (light gray and red lines, quantified in e) and HFD (black lines with boxes) conditions. Data are presented as mean ± SEM. *, P = 0.0444 (70 μm) and P = 0.0239 (130 μm); **, P = 0.0014 (40 μm), P = 0.0043 (60 μm), P = 0.0019 (100  μm), and P = 0.0088 (120 μm); ***, P = 0.0004 (110 μm) and P = 0.0005 (50 μm) relative to the value obtained with the respective control at the same time-point using two-way ANOVA, followed by Fisher’s LSD tests. n = 4 (CD) or 5 (HFD) animals per experimental group. i, j Energy expenditure (EE) corrected by total body weight (i) and lean mass (j) exhibited by CD-fed 3-month-old WT and Vav2^Onc/Onc (Onc) mice (bottom) during the indicated light cycle periods (inset). Data are shown as mean ± SEM. ***, P = 0.000004 (dark period) and 0.00007 (light period) using two-way ANOVA and Holm–Sidak multiple comparison tests (n = 12 animals per group). k RQ of CD-fed 3-month-old animals of the indicated genotypes (inset) during the indicated light cycle periods (bottom). Data are presented as mean ±  SEM. *, P = 0.0143 (light period) and 0.0499 (total) using two-way ANOVA and Holm–Sidak multiple comparison tests (n = 12 animals per group). Source data for this figure are provided as a Source data file.