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Horm Metab Res 2003; 35(4): 211-216
DOI: 10.1055/s-2003-39476
Original Basic
© Georg Thieme Verlag Stuttgart · New York

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

X.  Wang 1 , K.  McCormick 1 , G.  Mick 1
  • 1University of Alabama at Birmingham, Dept. of Pediatrics, Endocrinology, Birmingham, AL, USA
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Publication History

Received 14 October 2002

Accepted after Revision 9 December 2002

Publication Date:
02 June 2003 (online)

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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

References

  • 1 Castellot J, Karnovsky M, Spiegleman B. Potent stimulation of vascular endothelial cell growth by differentiated 3T3L1 cells.  Proc Natl Acad Sci. 1980;  77 6007-6011
    PubMedGoogle Scholar
  • 2 Silverman K. et al . Angiogenic activity of adipose tissue.  Biochem Biophys Res Comm. 1988;  153 347-352
    CrossrefPubMedGoogle Scholar
  • 3 Mandrup S. et al . Inhibition of 3T3-L1 adipocyte differentiation by expression of acyl-CoA-binding protein antisense RNA.  J Biol Chem. 1998;  273 (37) 23 897-23 903
    PubMedGoogle Scholar
  • 4 Claffey K P, Wilkison W O, Spiegelman B M. Vascular endothelial growth factor: regulation by cell differentiation and activated second messenger pathways.  J Biol Chem. 1992;  23 16 317-16 322
    PubMedGoogle Scholar
  • 5 Zhang Q X. et al . Vascular endothelial growth factor is the major angiogenic factor in omentum: mechanism of the omentum-mediated angiogenesis.  J Surg Res. 1997;  67 147-154
    CrossrefPubMedGoogle Scholar
  • 6 Asano A. et al . Adrenergic activation of vascular endothelial growth factor mRNA expression in rat brown adipose tissue: implication in cold-induced thermogenesis.  Biochem J. 1997;  328 179-183
    PubMedGoogle Scholar
  • 7 Hausman G J, Richardson R L. Cellular and vascular development in immature rat adipose tissue.  J Lipid Res. 1983;  24 522-532
    PubMedGoogle Scholar
  • 8 Crandall D, Hausman G, Kral J. A review of the microcirculation of adipose tissue: anatomic, metabolic and angiogenic perspectives.  Microcirculation. 1997;  4 211-230
    CrossrefPubMedGoogle Scholar
  • 9 Crandall D L, DiGirolamo M. Hemodynamic and metabolic correlates in adipose tissue: pathophysiologic considerations.  FASEB J. 1990;  4 141-147
    PubMedGoogle Scholar
  • 10 Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor.  Endocrine Reviews. 1997;  18 4-25
    CrossrefPubMedGoogle Scholar
  • 11 Yang R. et al . Effects of vascular endothelial growth factor on hemodynamics and cardiac performance.  J Cardiovasc Pharmacol. 1996;  27 838-844
    CrossrefPubMedGoogle Scholar
  • 12 Zachary I. Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor.  Am J Physiol Cell Physiol. 2001;  280 C1375-C1386
    PubMedGoogle Scholar
  • 13 Mick G, Wang X, McCormick K L. White adipocyte vascular endothelial growth factor (VEGF): regulation by insulin.  Endocrinology. 2002;  143 948-953
    CrossrefPubMedGoogle Scholar
  • 14 Roche E. et al . Palmitate and oleate induce the immediate-early response genes c-fos and nur-77 in the pancreatic beta-cell line INS-1.  Diabetes. 1999;  48 (10) 2007-2014
    PubMedGoogle Scholar
  • 15 de Boer S F. et al . Effects of fasting on plasma catecholamine, corticosterone and glucose concentrations under basal and stress conditions in individual rats.  Physiol Behav. 1989;  45 (5) 989-994
    CrossrefPubMedGoogle Scholar
  • 16 de Boer S F, van der Gugten J. Daily variations in plasma noradrenaline, adrenaline and corticosterone concentrations in rats.  Physiol Behav. 1987;  40 (3) 323-328
    CrossrefPubMedGoogle Scholar
  • 17 Yancopoulos G D. et al . Vascular-specific growth factors and blood vessel formation.  Nature. 2000;  407 242-248
    CrossrefPubMedGoogle Scholar
  • 18 Rosell S, Belfrage E. Blood circulation in adipose tissue.  Physiological reviews. 1979;  59 (4) 1078-1104
    PubMedGoogle Scholar
  • 19 DiGirolamo M. et al . Relationship of adipose tissue blood flow to fat cell size and number.  Am J Physiol. 1971;  220 932-937
    PubMedGoogle Scholar
  • 20 Gerber H P. et al . VEGF is required for growth and survival in neonatal mice.  Development. 1999;  126 (6) 1149-1159
    PubMedGoogle Scholar
  • 21 Cameliet P. Mechanisms of angiogenesis and arteriogenesis.  Nature Medicine,. 2000;  6 389-395
    CrossrefPubMedGoogle Scholar
  • 22 Wulff C. et al . Luteal angiogenesis: Prevention and intervention by treatment with vascular endothelial growth factor TrapA40.  J Clin Endo Metab. 2001;  86 3377-3386
    CrossrefPubMedGoogle Scholar
  • 23 Rupnick M A. et al . Adipose tissue mass can be regulated through the vasculature.  Proc Natl Acad Sci USA. 2002;  99 (16) 10 730-10 735
    PubMedGoogle Scholar
  • 24 Engeli S, Sharma A M. Role of adipose tissue for cardiovascular-renal regulation in health and disease.  Horm Metab Res. 2000;  32 (11 - 12) 485-499
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Hajri T, Abumrad N A. Fatty acid transport across membranes: relevance to nutrition and metabolic pathology.  Annu Rev Nutr. 2002;  22 383-415
    CrossrefPubMedGoogle Scholar
  • 26 Bartness T J, Bamshad M. Innervation of mammalian white adipose tissue: implications for the regulation of total body fat.  Am J Physiol. 1998;  275 (5 Pt 2) R1399-R1411
    PubMedGoogle Scholar
  • 27 Langin D, Lucas S, Lafontan M. Millennium fat-cell lipolysis reveals unsuspected novel tracks.  Horm Metab Res. 2000;  32 443-452
    PubMedGoogle Scholar
  • 28 Senger D R. et al . Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.  Science. 1983;  219 983-985
    CrossrefPubMedGoogle Scholar
  • 29 Bates D O, Curry F E. Vascular endothelial growth factor increases hydraulic conductivity of isolated perfused microvessels.  Am J Physiol. 1996;  271 (6 Pt 2) H2520-H2528
    PubMedGoogle Scholar
  • 30 Bates D O, Lodwick D, Williams B. Vascular endothelial growth factor and microvascular permeability.  Microcirculation,. 1999;  6 (2) 83-96
    CrossrefPubMedGoogle Scholar
  • 31 Hippenstiel S. et al . VEGF induces hyperpermeability by a direct action of endothelial cells.  Am J Physiol. 1998;  274 L678-L684
    PubMedGoogle Scholar
  • 32 LeCouter J, Ferrara N. EG-VEGF and the concept of tissue-specific angiogenic growth factors.  Semin Cell Dev Biol. 2002;  13 (1) 3-8
    CrossrefPubMedGoogle Scholar
  • 33 Semenza G. HIF-1: mediator of physiological and pathophysiological responses to hypoxia.  J Appl Physiol. 2000;  88 1474-1480
    PubMedGoogle Scholar
  • 34 Kvietikova I. et al . The hypoxia-inducible factor-1 DNA recognition site is cAMP-responsive.  Kidney Int. 1997;  51 (2) 564-566
    PubMedGoogle Scholar
  • 35 Firth J D, Ebert B L, Ratcliffe P J. Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements.  J Biol Chem. 1995;  270 (36) 21 021-21 027
    PubMedGoogle Scholar
  • 36 Thacker S V, Nickel M, DiGirolamo M. Effects of food restriction on lactate production from glucose by rat adipocytes.  Am J Physiol. 1987;  253 (4 Pt 1) E336-E342
    PubMedGoogle Scholar
  • 37 Newby F D. et al . Adipocyte lactate production remains elevated during refeeding after fasting.  Am J Physiol. 1990;  259 (6 Pt 1) E865-E871
    PubMedGoogle Scholar
  • 38 Dantz D. et al . Vascular endothelial growth factor: a novel endocrine defensive response to hypoglycemia.  J Clin Endocrinol Metab. 2002;  87 (2) 835-840
    CrossrefPubMedGoogle Scholar
  • 39 Brooks S E. et al . Modulation of VEGF production by pH and glucose in retinal Muller cells.  Curr Eye Res. 1998;  17 (9) 875-882
    CrossrefPubMedGoogle Scholar
  • 40 Dallman M F. et al . Starvation: early signals, sensors, and sequelae.  Endocrinology,. 1999;  140 (9) 4015-4023
    CrossrefPubMedGoogle Scholar
  • 41 Hanson E S, Levin N, Dallman M F. Elevated corticosterone is not required for the rapid induction of neuropeptide Y gene expression by an overnight fast.  Endocrinology. 1997;  138 (3) 1041-1047
    CrossrefPubMedGoogle Scholar
  • 42 Tonello C. et al . Role of sympathetic activity in controlling the expression of vascular endothelial growth factor in brown fat cells of lean and genetically obese rats.  FEBS Lett. 1999;  442 (2 - 3) 167-172
    CrossrefPubMedGoogle Scholar
  • 43 Vernon R G, Clegg R A. 1985 The metabolism of white adipose tissue in vivo and in vitro. In: New Perspectives in Adipose Tissue: Structure, Function and Development. A. Cryer and R.L.R. Van, eds. London; Butterworth and Co Ltd 65-81
    Google Scholar
  • 44 Brausewetter F. et al . Microvascular permeability is increased in both types of diabetes and correlates differentially with serum levels of insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF).  Horm Metab Res. 2001;  33 (12) 713-720
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Miyazawa S. et al . Increase in serum vascular endothelial growth factor in obese subjects:relationship to body fat distribution.  Diabetes. 2002;  51 (Supplement 2) A404-A405
    PubMedGoogle Scholar
  • 46 Keyt B A. et al . The carboxyl-terminal domain (111 - 165) of vascular endothelial growth factor is critical for its mitogenic potency.  J Biol Chem. 1996;  271 (13) 7788-7795
    CrossrefPubMedGoogle Scholar
  • 47 Iozzo R V, San A ntonio. Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena.  J Clin Invest. 2001;  108 (3) 349-355
    CrossrefPubMedGoogle Scholar

G. Mick

University of Alabama at Birmingham · Dept. of Pediatrics · Endocrinology

1600 7th Ave South ACC 608 · Birmingham · AL 35233 · USA ·

Phone: +1 (205) 939-52 98

Fax: +1 (205) 939-98 21

Email: gmick@peds.uab.edu

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