title: Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues.
abstract: Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti- VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Honek
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;
authors.forename: Takahiro
authors.initials: T
authors.lastname: Seki
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;
authors.forename: Hideki
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;
authors.forename: Carina
authors.initials: C
authors.lastname: Fischer
authors.affiliation: Simcere Pharmaceutical Research and Development, Nanjing, Jiangsu 210042, China;
authors.forename: Jingrong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;
authors.forename: Sharon
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, United Kingdom; and.
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.affiliation: Simcere Pharmaceutical Research and Development, Nanjing, Jiangsu 210042, China;
authors.forename: Jingwu
authors.initials: J
authors.lastname: Zang
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden; Department of Cardiovascular Sciences, University of Leicester and National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, United Kingdom; and Department of Medicine and Health Sciences, Linköping University, 581 83 Linköping, Sweden yihai.cao@ki.se.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
mesh_terms: D017667:Adipocytes / Q000473:pathology; D002001:Adipose Tissue, Brown / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D052436:Adipose Tissue, White / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D000375:Aging / Q000473:pathology*; D000818:Animals; D048429:Cell Size; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D008055:Lipids; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: aging; angiogenesis; endothelial cells; metabolic disorders; vascularization