title: Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis.
abstract: Vascular endothelial growth factor A (VEGF) is highly expressed in adipose tissue. Its role, however, has not been fully elucidated. Here, we reveal the metabolic role of adipose-VEGF by studying mice with deletion (VEGF(AdΔ)) or doxycycline-inducible overexpression of a VEGF transgene (VEGF(AdTg)) in the adipose tissue. VEGF(AdΔ) mice have reduced adipose vascular density and show adipose hypoxia, apoptosis, inflammation, and metabolic defects on a high-fat diet. In contrast, induction of VEGF expression in VEGF(AdTg) mice leads to increased adipose vasculature and reduced hypoxia. The latter changes are sufficient to counteract an established compromising effect of high-fat diet on the metabolism, indicating that metabolic misbalance is reversible by adipose vessel density increase. Our data clearly show the essential role of VEGF signaling for adequate adipose function. Besides revealing insights into the molecular mechanisms of obesity-related metabolic diseases, this study points to the therapeutic potential of increased adipose angiogenesis.
authors: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5T 3H7, Canada.
authors: Hoon-Ki
authors: HK
authors: Sung
authors: Kyung-Oh
authors: KO
authors: Doh
authors: Joe Eun
authors: JE
authors: Son
authors: Jin Gyoon
authors: JG
authors: Park
authors: Yunui
authors: Y
authors: Bae
authors: Soojeong
authors: S
authors: Choi
authors: Seana Mary Lunney
authors: SM
authors: Nelson
authors: Rebecca
authors: R
authors: Cowling
authors: Kristina
authors: K
authors: Nagy
authors: Iacovos P
authors: IP
authors: Michael
authors: Gou Young
authors: GY
authors: Koh
authors: S Lee
authors: SL
authors: Adamson
authors: Tony
authors: T
authors: Pawson
authors: Andras
authors: A
authors: Nagy
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D059305:Diet, High-Fat; D004318:Doxycycline / Q000494:pharmacology; D018149:Glucose Intolerance / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D054392:Adipokines; D042461:Vascular Endothelial Growth Factor A; D004318:Doxycycline