Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure

Kai Sun, Christine M. Kusminski, Kate Luby-Phelps, Stephen B. Spurgin, Yu A. An, Qiong A. Wang, William L. Holland, Philipp E. Scherer

Research output: Contribution to journalArticle

56 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)474-483
Number of pages10
JournalMolecular Metabolism
Volume3
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Brown Adipose Tissue
Energy Metabolism
Vascular Endothelial Growth Factor A
Brown Adipocytes
White Adipose Tissue
Diet
Obese Mice
Thermogenesis
Doxycycline
High Fat Diet
Lipid Metabolism
Transgenic Mice
Up-Regulation
Obesity
Phenotype
Glucose

Keywords

  • BAT
  • Cold tolerance
  • Energy expenditure
  • VEGF-A

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure. / Sun, Kai; Kusminski, Christine M.; Luby-Phelps, Kate; Spurgin, Stephen B.; An, Yu A.; Wang, Qiong A.; Holland, William L.; Scherer, Philipp E.

In: Molecular Metabolism, Vol. 3, No. 4, 2014, p. 474-483.

Research output: Contribution to journalArticle

@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.}",
year = "2014",
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",

}

TY - JOUR

T1 - Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure

AU - Sun, Kai

AU - Kusminski, Christine M.

AU - Luby-Phelps, Kate

AU - Spurgin, Stephen B.

AU - An, Yu A.

AU - Wang, Qiong A.

AU - Holland, William L.

AU - Scherer, Philipp E.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - BAT

KW - Cold tolerance

KW - Energy expenditure

KW - VEGF-A

UR - http://www.scopus.com/inward/record.url?scp=84902356732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902356732&partnerID=8YFLogxK

U2 - 10.1016/j.molmet.2014.03.010

DO - 10.1016/j.molmet.2014.03.010

M3 - Article

VL - 3

SP - 474

EP - 483

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

IS - 4

ER -