title: Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance.
abstract: During the expansion of fat mass in obesity, vascularization of adipose tissue is insufficient to maintain tissue normoxia. Local hypoxia develops and may result in altered adipokine expression, proinflammatory macrophage recruitment, and insulin resistance. We investigated whether an increase in adipose tissue angiogenesis could protect against obesity-induced hypoxia and, consequently, insulin resistance. Transgenic mice overexpressing vascular endothelial growth factor (VEGF) in brown adipose tissue (BAT) and white adipose tissue (WAT) were generated. Vessel formation, metabolism, and inflammation were studied in VEGF transgenic mice and wild-type littermates fed chow or a high-fat diet. Overexpression of VEGF resulted in increased blood vessel number and size in both WAT and BAT and protection against high-fat diet-induced hypoxia and obesity, with no differences in food intake. This was associated with increased thermogenesis and energy expenditure. Moreover, whole-body insulin sensitivity and glucose tolerance were improved. Transgenic mice presented increased macrophage infiltration, with a higher number of M2 anti-inflammatory and fewer M1 proinflammatory macrophages than wild-type littermates, thus maintaining an anti-inflammatory milieu that could avoid insulin resistance. These studies suggest that overexpression of VEGF in adipose tissue is a potential therapeutic strategy for the prevention of obesity and insulin resistance.
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Ivet
authors.initials: I
authors.lastname: Elias
authors.forename: Sylvie
authors.initials: S
authors.lastname: Franckhauser
authors.forename: Tura
authors.initials: T
authors.lastname: Ferré
authors.forename: Laia
authors.initials: L
authors.lastname: Vilà
authors.forename: Sabrina
authors.initials: S
authors.lastname: Tafuro
authors.forename: Sergio
authors.initials: S
authors.lastname: Muñoz
authors.forename: Carles
authors.initials: C
authors.lastname: Roca
authors.forename: David
authors.initials: D
authors.lastname: Ramos
authors.forename: Anna
authors.initials: A
authors.lastname: Pujol
authors.forename: Efren
authors.initials: E
authors.lastname: Riu
authors.forename: Jesús
authors.initials: J
authors.lastname: Ruberte
authors.forename: Fatima
authors.initials: F
authors.lastname: Bosch
mesh_terms: D002001:Adipose Tissue, Brown / Q000098:blood supply* / Q000502:physiology; D052436:Adipose Tissue, White / Q000098:blood supply* / Q000502:physiology; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D018149:Glucose Intolerance / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000503:physiopathology*; D022722:Thermogenesis / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse