A Better Way to Get Fat?

Science Signaling  17 Apr 2012:
Vol. 5, Issue 220, pp. ec112
DOI: 10.1126/scisignal.2003142

White adipose tissue that expands because of obesity is hypoxic because of poor vascularization and may show fibrosis and inflammation, whereas white adipose tissue that expands in a “healthy” manner is appropriately vascularized and thus nonhypoxic, as well as less fibrotic and inflamed. Sun et al. examined the role of angiogenesis mediated by vascular endothelial growth factor A (VEGF-A) during expansion of the white adipose tissue. In mice overexpressing VEGF-A through the promoter encoding adiponectin (a hormone produced by white adipose tissue), increased abundance of VEGF-A was detected primarily in white adipose tissue and to a lesser extent in brown adipose tissue, which is more metabolically active than white adipose tissue. Compared with controls, mice overexpressing VEGF-A showed better glucose tolerance and insulin sensitivity, increased lipid clearance, decreased incidence of fatty liver (hepatic steatosis), and increased energy expenditure when fed a high-fat diet. At the cellular level, adipocytes from the VEGF-A–overexpressing mice were smaller in size and had reduced lipid depots. Furthermore, they showed increased abundance of PGC-1α and UCP-1 (two proteins that are abundant in brown adipose tissue) and decreased abundance of HIF-1α (a transcription factor induced by hypoxia) and fibrotic collagens. Wild-type mice treated with Mcr84 (a monoclonal antibody against VEGF that antagonizes VEGF function) just before and during high-fat feeding showed decreased insulin sensitivity and decreased lipid clearance. Thus, VEGF-mediated angiogenesis in white adipose tissue can attenuate some of the metabolic effects of diet-induced obesity.

K. Sun, I. Wernstedt Asterholm, C. M. Kusminski, A. C. Bueno, Z. V. Wang, J. W. Pollard, R. A. Brekken, P. E. Scherer, Dichotomous effects of VEGF-A on adipose tissue dysfunction. Proc. Natl. Acad. Sci. U.S.A. 109, 5874–5879 (2012). [Abstract] [Full Text]