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 language | English (US) |
|---|---|
| Pages (from-to) | 474-483 |
| Number of pages | 10 |
| Journal | Molecular Metabolism |
| Volume | 3 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2014 |
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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 journal › Article
}
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
C2 - 24944907
AN - SCOPUS:84902356732
VL - 3
SP - 474
EP - 483
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
IS - 4
ER -