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: Jennifer Honek, Takahiro Seki, Hideki Iwamoto, Carina Fischer, Jingrong Li, Sharon Lim, Nilesh J Samani, Jingwu Zang, Yihai Cao
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 41 Pg. 14906-11 (Oct 14 2014) ISSN: 1091-6490 [Electronic] United States
• PMID: 25271320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipids
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Adipocytes (pathology)
• Adipose Tissue, Brown (blood supply, pathology, physiopathology)
• Adipose Tissue, White (blood supply, pathology, physiopathology)
• Aging (pathology)
• Animals
• Cell Size
• Cell Survival (drug effects)
• Female
• Insulin Resistance
• Lipids (blood)
• Mice, Inbred C57BL
• Obesity (blood, pathology)
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor A (metabolism, pharmacology)
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)