Sci. Signal., 17 April 2012
Physiology A Better Way to Get Fat?
Science Signaling, AAAS, Washington, DC 20005, USA
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]
Citation: W. Wong, A Better Way to Get Fat? Sci. Signal. 5, ec112 (2012).
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