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Cell Metab. 2016 Apr 12;23(4):712-24. doi: 10.1016/j.cmet.2016.03.004.

VEGFB/VEGFR1-Induced Expansion of Adipose Vasculature Counteracts Obesity and Related Metabolic Complications.

Author information

1
Wihuri Research Institute and Translational Cancer Biology Program, University of Helsinki, Biomedicum Helsinki, 00290 Helsinki, Finland. Electronic address: marius.robciuc@helsinki.fi.
2
Wihuri Research Institute and Translational Cancer Biology Program, University of Helsinki, Biomedicum Helsinki, 00290 Helsinki, Finland.
3
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
4
Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands.
5
Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands.
6
Oulu Center for Cell-Matrix Research and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Biocenter Oulu, 90220 Oulu, Finland.
7
Department of Biosciences and Physiology and Neuroscience, University of Helsinki, Biocenter 3, 00790 Helsinki, Finland.
8
Biomedicum Imaging Unit, University of Helsinki, Biomedicum Helsinki, 00290 Helsinki, Finland.
9
Department of Pediatrics, Center for Liver Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands.
10
Wihuri Research Institute and Translational Cancer Biology Program, University of Helsinki, Biomedicum Helsinki, 00290 Helsinki, Finland. Electronic address: kari.alitalo@helsinki.fi.

Abstract

Impaired angiogenesis has been implicated in adipose tissue dysfunction and the development of obesity and associated metabolic disorders. Here, we report the unexpected finding that vascular endothelial growth factor B (VEGFB) gene transduction into mice inhibits obesity-associated inflammation and improves metabolic health without changes in body weight or ectopic lipid deposition. Mechanistically, the binding of VEGFB to VEGF receptor 1 (VEGFR1, also known as Flt1) activated the VEGF/VEGFR2 pathway and increased capillary density, tissue perfusion, and insulin supply, signaling, and function in adipose tissue. Furthermore, endothelial Flt1 gene deletion enhanced the effect of VEGFB, activating the thermogenic program in subcutaneous adipose tissue, which increased the basal metabolic rate, thus preventing diet-induced obesity and related metabolic complications. In obese and insulin-resistant mice, Vegfb gene transfer, together with endothelial Flt1 gene deletion, induced weight loss and mitigated the metabolic complications, demonstrating the therapeutic potential of the VEGFB/VEGFR1 pathway.

PMID:
27076080
PMCID:
PMC5898626
DOI:
10.1016/j.cmet.2016.03.004
[Indexed for MEDLINE]
Free PMC Article

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