Nutritional Regulation of White Adipocyte Vascular Endothelial Growth Factor (VEGF)

Abstract

White adipose tissue has distinctive angiogenic properties. White adipocytes are capable of producing vascular endothelial growth factor (VEGF) in response to insulin and catecholamines. Recognizing the dual functions of adipose tissue as an endocrine/metabolic organ and fuel storage depot with an inimitable ability to adjust its organ mass, our aim was to determine whether fasting would affect adipocyte VEGF₁₆₅ production. Rats were fed ad libitum, then fasted for 24 hours, and then refed after the 24-hour fast. The isolated white adipocytes from each group and blood endocrine/metabolic profiles were examined at each stage, yielding three sets of results. Using cultured adipocytes, fasting caused a two-fold increase in VEGF₁₆₅ formation compared to fed rats that normalized after refeeding. Likewise, freshly prepared adipocytes manifested a three-fold augmentation in adipocyte VEGF₁₆₅ mRNA expression and a 60 % increase the transcriptional regulator hypoxia-inducible factor 1 (HIF-1α) that normalized after refeeding. Blood studies revealed the expected fasting-related alterations in glucose, β-hydroxybutyrate and corticosterone. Plasma VEGF concentrations were attenuated by 26 % with fasting, and did not normalize with refeeding. Multiple linear regression analyses uncovered statistically significant inverse correlations between plasma VEGF and blood β-hydroxybutyrate or serum corticosterone. Blood glucose, in contrast, correlated directly with plasma VEGF. We will discuss the potential role of enhanced adipocyte VEGF formation during starvation in light of the known actions of this factor on vascular endothelial mitogenesis and permeability.

Key words

Fasting - Adipose tissue - Vascular permeability - Hypoxia-inducible factor 1

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