Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues
2014 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 41, 14906-14911 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
National Academy of Sciences , 2014. Vol. 111, no 41, 14906-14911 p.
angiogenesis; aging; endothelial cells; metabolic disorders; vascularization
IdentifiersURN: urn:nbn:se:liu:diva-112036DOI: 10.1073/pnas.1415825111ISI: 000342922000067PubMedID: 25271320OAI: oai:DiVA.org:liu-112036DiVA: diva2:763903
Funding Agencies|Swedish Research Council; Swedish Cancer Foundation; Karolinska Institute Foundation; Karolinska Institute Distinguished Professor Award; Torsten Soderbergs Foundation; Novo Nordisk Foundation; European Research Council Advanced Grant ANGIOFAT 2014-11-172014-11-132014-11-17