title: Inhibitor of differentiation-3 mediates high fat diet-induced visceral fat expansion.
abstract: OBJECTIVE
  Inhibitor of differentiation-3 (Id3) has been implicated in promoting angiogenesis, a key determinant of high-fat diet (HFD)-induced visceral adiposity. Yet the role of Id3 in HFD-induced angiogenesis and visceral adipose expansion is unknown.
  
  
  RESULTS
  Id3(-/-) mice demonstrated a significant attenuation of HFD-induced visceral fat depot expansion compared to wild type littermate controls. Importantly, unlike other Id proteins, loss of Id3 did not affect adipose depot size in young mice fed chow diet or differentiation of adipocytes in vitro or in vivo. Contrast enhanced ultrasound revealed a significant attenuation of visceral fat microvascular blood volume in HFD-fed mice null for Id3 compared to wild type controls. HFD induced Id3 and VEGFA expression in the visceral stromal vascular fraction and Id3(-/-) mice had significantly lower levels of VEGFA protein in visceral adipose tissue compared to wild type. Furthermore, HFD-induced VEGFA expression in visceral adipose tissue was completely abolished by loss of Id3. Consistent with this effect, Id3 abolished E12-mediated repression of VEGFA promoter activity.
  
  
  CONCLUSIONS
  Results identify Id3 as an important regulator of HFD-induced visceral adipose VEGFA expression, microvascular blood volume, and depot expansion. Inhibition of Id3 may have potential as a therapeutic strategy to limit visceral adiposity.
authors.affiliation: MR5 G133, Robert M. Berne Cardiovascular Research Center, 415 Lane Rd, Charlottesville, VA 22908, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Cutchins
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Harmon
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kirby
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Doran
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Oldham
authors.forename: Marcus
authors.initials: M
authors.lastname: Skaflen
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Klibanov
authors.forename: Nahum
authors.initials: N
authors.lastname: Meller
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Keller
authors.forename: James
authors.initials: J
authors.lastname: Garmey
authors.forename: Coleen A
authors.initials: CA
authors.lastname: McNamara
mesh_terms: D017667:Adipocytes / Q000473:pathology; D050154:Adiposity / Q000502:physiology*; D000818:Animals; D001810:Blood Volume / Q000502:physiology; D004041:Dietary Fats / Q000494:pharmacology*; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D051796:Inhibitor of Differentiation Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C067679:Idb3 protein, mouse
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