Adipose tissue mass can be regulated through the vasculature.
Tumor growth is angiogenesis dependent. We hypothesized that nonneoplastic tissue growth also depends on neovascularization. We chose adipose tissue as an experimental system because of its remodeling capacity. Mice from different obesity models received anti-angiogenic agents. Treatment resulted in dose-dependent, reversible weight reduction and adipose tissue loss. Marked vascular remodeling was evident in adipose tissue sections, which revealed decreased endothelial proliferation and increased apoptosis in treated mice compared with controls. Continuous treatment maintained mice near normal body weights for age without adverse effects. Metabolic adaptations in food intake, metabolic rate, and energy substrate utilization were associated with anti-angiogenic weight loss. We conclude that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature.
Rupnick
Maria A
MA
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. rupnick@hub.tch.harvard.edu
Panigrahy
Dipak
D
Zhang
Chen-Yu
CY
Dallabrida
Susan M
SM
Lowell
Bradford B
BB
Langer
Robert
R
Folkman
M Judah
MJ
D000273:Adipose Tissue / Q000098:blood supply* / Q000187:drug effects; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D043168:Angiostatins; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001713:Biphenyl Compounds; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D003510:Cyclohexanes; D004195:Disease Models, Animal; D043169:Endostatins; D004734:Energy Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D009930:Organic Chemicals; D010446:Peptide Fragments / Q000494:pharmacology; D010654:Phenylbutyrates; D010958:Plasminogen / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology; D013792:Thalidomide / Q000494:pharmacology; D013997:Time Factors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D003510:Cyclohexanes; D043169:Endostatins; D009930:Organic Chemicals; D010446:Peptide Fragments; D010654:Phenylbutyrates; D012717:Sesquiterpenes; D013792:Thalidomide; D043168:Angiostatins; D010958:Plasminogen; D003094:Collagen; C113281:Bay 12-9566; D000077609:O-(Chloroacetylcarbamoyl)fumagillol