title: Loss of Adipocyte VEGF Impairs Endurance Exercise Capacity in Mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1Division of Exercise Physiology, School of Medicine, West Virginia University, Morgantown, WV; 2Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV; 3Biomedical Sciences Program, School of Medicine, West Virginia University, Morgantown, WV; 4Department of Surgery, School of Medicine, West Virginia University, Morgantown, WV; 5Mary Babb Randolph Cancer Center, School of Medicine, West Virginia University, Morgantown, WV; and 6Center for Cardiovascular and Respiratory Sciences, School of Medicine, West Virginia University, Morgantown, WV.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Zachwieja
authors.forename: Grant C
authors.initials: GC
authors.lastname: O'Connell
authors.forename: Janelle C
authors.initials: JC
authors.lastname: Stricker
authors.forename: Jessica
authors.initials: J
authors.lastname: Allen
authors.forename: Linda
authors.initials: L
authors.lastname: Vona-Davis
authors.forename: Randall
authors.initials: R
authors.lastname: Bryner
authors.forename: William
authors.initials: W
authors.lastname: Mandler
authors.forename: I Mark
authors.initials: IM
authors.lastname: Olfert
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002197:Capillary Action; D017079:Exercise Tolerance / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000097:blood; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012420:Running / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D042461:Vascular Endothelial Growth Factor A; D005990:Glycerol