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Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure
- Source :
- Molecular Metabolism
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
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 in vivo. 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.
- Subjects :
- Genetically modified mouse
HFD, high-fat diet
medicine.medical_specialty
UCP1, uncoupling protein1
OGTT, oral glucose tolerance test
Transgene
White adipose tissue
Biology
Brief Communication
Cold tolerance
VEGF-A
03 medical and health sciences
0302 clinical medicine
Internal medicine
Brown adipose tissue
medicine
PGC-1α, PPARγ co-activator-1α
OCR, oxygen consumption rate
HIF1, hypoxia-induced factor1
Dox, doxycycline
Molecular Biology
030304 developmental biology
Doxycycline
0303 health sciences
BAT
WAT, white adipose tissue
Lipid metabolism
Cell Biology
Phenotype
BAT, brown adipose tissue
medicine.anatomical_structure
Endocrinology
030220 oncology & carcinogenesis
Energy expenditure
Thermogenesis
medicine.drug
Subjects
Details
- ISSN :
- 22128778
- Volume :
- 3
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular Metabolism
- Accession number :
- edsair.doi.dedup.....571a3548efcda65e0b3f2052add0a9f9
- Full Text :
- https://doi.org/10.1016/j.molmet.2014.03.010