@article{49904385e8d7472fba8e9add4da0eace,
title = "Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure",
abstract = "We recently reported that local overexpression of VEGF-A in white adipose tissue (WAT) protects against diet-induced obesity and metabolic dysfunction. The observation that VEGF-A induces a {"}brown adipose tissue (BAT)-like{"} phenotype in WAT prompted us to further explore the direct function of VEGF-A in BAT. We utilized a doxycycline (Dox)-inducible, brown adipocyte-specific VEGF-A transgenic overexpression model to assess direct effects of VEGF-A in BAT invivo. We observed that BAT-specific VEGF-A expression increases vascularization and up-regulates expression of both UCP1 and PGC-1α in BAT. As a result, the transgenic mice show increased thermogenesis during chronic cold exposure. In diet-induced obese mice, introducing VEGF-A locally in BAT rescues capillary rarefaction, ameliorates brown adipocyte dysfunction, and improves deleterious effects on glucose and lipid metabolism caused by a high-fat diet challenge. These results demonstrate a direct positive role of VEGF-A in the activation and expansion of BAT.",
keywords = "BAT, Cold tolerance, Energy expenditure, VEGF-A",
author = "Kai Sun and Kusminski, {Christine M.} and Kate Luby-Phelps and Spurgin, {Stephen B.} and An, {Yu A.} and Wang, {Qiong A.} and Holland, {William L.} and Scherer, {Philipp E.}",
note = "Funding Information: We thank Dr. Robert A. Koza at the Pennington Biomedical Research Center for the UCP1 promoter fragment and Dr. Jeffrey Pollard from the MRC Centre for Reproductive Health at the University of Edinburgh for the TRE-VEGF mice. We also thank Angelica Sifuentes, Amy Song, and Steven Connell in the Scherer laboratory for technical help; John Sheldon from the pathology core facility at the University of Texas (UT) Southwestern for help with histology; Dr. Bob Hammer and the transgenic core facility at UT Southwestern for generating the UCP1-rtTA transgenic mice; the Metabolic Core Unit at UT Southwestern for phenotyping efforts. This work was supported by National Institutes of Health Grants R01-DK55758 , R01-DK099110 and P01DK088761 (to P.E.S.). Q.A.W. is supported by a postdoctoral fellowship from the ADA ( 7-11-MN-47 ). C.M.K. is supported by was supported by a fellowship from the Juvenile Diabetes Research Foundation International (JDRF 3-2008-130 ). W.L.H. is supported by National Institutes of Health Grant ( R00-DK094973 ) and AHA Beginning Grant in Aid 12BGI-A8910006 . ",
year = "2014",
month = jul,
doi = "10.1016/j.molmet.2014.03.010",
language = "English (US)",
volume = "3",
pages = "474--483",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier GmbH",
number = "4",
}