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Biosci Rep. 2017 Aug 10. pii: BSR20171089. doi: 10.1042/BSR20171089. [Epub ahead of print]

The Role of Vascular Endothelial Growth Factor-B in Metabolic Homeostasis: Current Evidence.

Author information

1
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277, Jiefang Avenue, Wuhan, N/A, 430022, China.
2
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
3
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China cheria_chen@126.com.

Abstract

It has been shown that adipose tissue and skeletal muscles of lean individuals respond to meal-induced hyperinsulinemia by increases in perfusion, the effect not observed in patients with metabolic syndrome. In conditions of hyperglycaemia and hypertriglyceridemia, this insufficient vascularization leads to the liberation of reactive oxygen species, and disruption of nitric oxide synthesis and endothelial signalling responsible for the uptake of circulating fatty acids, whose accumulation in skeletal muscles and adipose tissue is widely associated with impairment of insulin signalling. While the angiogenic role of VEGF-A and its increased circulating concentrations in obesity have been widely confirmed, the data related to the metabolic role of VEGF-B are diverse. However, recent discoveries indicate that this growth factor may be a promising therapeutic agent in patients with metabolic syndrome. Preclinical studies agree over two crucial metabolic effects of VEGF-B: a) regulation of fatty acids uptake and b) regulation of tissue perfusion via activation of VEGF-A/VEGFR2 pathway. While in some preclinical high-fat diet studies VEGF-B overexpression reverted glucose intolerance and stimulated fat burning, in others it furtherly promoted accumulation of lipids and lipotoxicity. Data from clinical studies point out the changes in circulating or tissue expression levels of VEGF-B in obese versus lean patients. Potentially beneficial effects of VEGF-B, achieved through enhanced blood flow (increased availability of insulin and glucose uptake in target organs) and decreased fatty acids uptake (prevention of lipotoxicity and improved insulin signalling), and its safety for clinical use, remain to be clarified through future translational research.

KEYWORDS:

VEGF-B; fatty acids; insulin resistance; metabolic syndrome; obesity; type 2 diabetes

PMID:
28798193
DOI:
10.1042/BSR20171089
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