Journal: iScience

Article Title: Angiogenesis-independent VEGF signaling enhances exercise capacity by increasing fat oxidation in mice fed sulfur amino acid-restricted diets

doi: 10.1016/j.isci.2025.114148

Figure Lengend Snippet: Inhibition of VEGFR signaling blocks increased endurance exercise capacity by SAAR (A) Fold changes of transcripts associated with Vegf signaling using transcriptomic dataset presented in in muscles of male mice ( n = 6) after sulfur amino acid restriction (SAAR) compared with control (Con) diet for seven days. (B) Normalized count values of Vegfb in EDL and soleus from bulk RNA sequencing ( n = 6) of male mice given ad libitum access to SAAR versus Con diet on day seven using transcriptomic dataset presented in . (C) Normalized count values of Flt1 in EDL and soleus from bulk RNA sequencing ( n = 6) of male mice given ad libitum access to SAAR versus Con diet on day seven using transcriptomic dataset presented in . (D) Experimental set up and color scheme used in E, 5F, C, and S5D. (E) Percent change in body weight ( n = 16–24) of male mice treated with vehicle (veh) or axitinib via oral gavage in combination with ad libitum access to SAAR versus Con diet after seven days. (F) Distance ran during a one-time maximal endurance test ( n = 16–24) of male mice treated with veh or axitinib via oral gavage in combination with ad libitum access to SAAR versus Con diet for seven days. (G) Representative fluorescence images of IB4 (white) staining in EDL cross sections of mice fed a Con or SAAR Diet, co-treated with veh or axitinib via oral gavage (scale bar, 400 μm) for seven days (n = 5–8). (H) Normalized count values of Flt1 in EDL treated with either veh or axitinib from bulk RNA sequencing ( n = 5) of male mice given ad libitum access to SAAR versus Con diet on day seven. (I) Normalized count values of Kdr in EDL treated with either veh or axitinib from bulk RNA sequencing ( n = 5) of male mice given ad libitum access to SAAR versus Con diet on day seven. (J) Experimental set up and color scheme used in K, 5L, J, and S5K. (K) Percent change in body weight (n = 8–10) of male mice treated with IgG or DC101 via i.p. injection every other day in combination with ad libitum access to SAAR versus Con diet after seven days. (L) Distance ran during a one-time maximal endurance test ( n = 12–16) of male mice treated with IgG or DC101 via i.p. injection every other day in combination with ad libitum access to SAAR versus Con diet on day seven. A-C, E, G-I, represent data from mice that were not subjected to endurance running; F, K, and L represent data from mice subjected to maximal endurance testing. All data are shown as mean, and error bars indicate SD unless otherwise noted; p values indicate the significance of the difference by two-way ANOVA with Sidak multiple comparisons test between diets and treatment; significance is determined by p < 0.05. See also and .

Article Snippet: Mouse (IgG2b) Myosin Heavy Chain Type I antibody (BA-F8) , DSHB , Cat# BA-F8; RRID: AB_10572253.

Techniques: Inhibition, Muscles, Control, RNA Sequencing, Fluorescence, Staining, Injection