Loss of Adipocyte VEGF Impairs Endurance Exercise Capacity in Mice.

Abstract

Reducing vascular endothelial growth factor (VEGF) in adipose tissue alters adipose vascularity and metabolic homeostasis. We hypothesized that this would also affect metabolic responses during exercise-induced stress and that adipocyte-specific VEGF-deficient (adipoVEGF-/-) mice would have impaired endurance capacity. Endurance exercise capacity in adipoVEGF-/- (n = 10) and littermate control (n = 11) mice was evaluated every 4 wk between 6 and 24 wk of age using a submaximal endurance run to exhaustion at 20 m·min(-1) at 10° incline. Maximal running speed, using incremental increases in speed at 30-s intervals, was tested at 25 and 37 wk of age. White and brown adipose tissue capillarity were reduced by 40% in adipoVEGF-/-, and no difference in skeletal muscle capillarity was observed. Endurance run time to exhaustion was 30% lower in adipoVEGF-/- compared with that in controls at all time points (P < 0.001), but no difference in maximal running speed was observed between the groups. After exercise (1 h at 50% maximum running speed), adipoVEGF-/- mice displayed lower circulating insulin (P < 0.001), lower glycerol (P < 0.05), and tendency for lower blood glucose (P = 0.06) compared with controls. There was no evidence of altered oxidative damage or changes in carnitine palmitoyltransferase-1β expression in skeletal muscle of adipoVEGF-/- mice. These data suggest that VEGF-mediated deficits in adipose tissue blunt the availability of lipid substrates during endurance exercise, which likely reduced endurance performance. Surprisingly, we also found an unchanged basal blood glucose despite lower circulating insulin in adipoVEGF-/- mice, suggesting that loss of adipocyte VEGF can blunt insulin release and/or increase basal insulin sensitivity.