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Diabetologia
Published in: Diabetologia 11/2003

01-11-2003 | Article

Elevated serum vascular endothelial growth factor is associated with visceral fat accumulation in human obese subjects

Authors: S. Miyazawa-Hoshimoto, Dr. K. Takahashi, H. Bujo, N. Hashimoto, Y. Saito

Published in: Diabetologia | Issue 11/2003

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Abstract

Aims/hypothesis

Adipose tissue expresses some bioactive molecules, which may be involved in the development of obesity-associated metabolic disorders and cardiovascular diseases. Vascular endothelial growth factor (VEGF) an important angiogenic factor is implicated in normal and pathological vessel formation. The aim of this study is to investigate clinically the association between blood serum VEGF concentrations and body fat accumulation as well as distribution. The study also aims to show the effect of serum VEGF protein on gene expression of transcriptional factor E26 transformation-specific-1 (Ets-1) and matrix metalloproteinase (MMP)-3.

Methods

Serum VEGF concentrations were measured in 38 overweight or obese subjects. Fat distribution in the abdominal subcutaneous as well as visceral fat areas was assessed by computed tomography scans at umbilical level. Furthermore, the changes of serum VEGF concentrations following body weight reduction therapy were analyzed in eight subjects recruited from the original pool of subjects. Semi-purified circulating VEGF proteins were obtained by heparin-sepharose and its biological activities were shown to alter gene expressions in human aortic endothelial cells.

Results

Serum VEGF concentrations were positively correlated with BMI (r=0.433, p=0.007) and visceral fat area (r=0.488, p=0.002). Stepwise regression analysis showed the visceral fat area as the most important determinant factor for VEGF circulating levels. Following body weight reduction therapy, VEGF concentrations as well as visceral fat area were decreased. The serum semi-purified VEGF protein enhanced expressions of Ets-1 and MMP-3 in human aortic endothelial cells.

Conclusion/interpretation

Increased serum VEGF concentrations associated with visceral fat accumulation could influence vascular endothelial function.
Literature
1.
MacDougald OA, Hwang CS, Fan H, Lane MD (1995) Regulation of the obese gene product (Leptin) in white adipose tissue and 3T3 adipocytes. Proc Natl Acad Sci USA 92:9034–9037PubMed
2.
Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV (1996) Leptin: the tale of an obesity gene. Diabetes 45:1455–1462PubMed
3.
Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91
4.
Shimomura I, Funahashi T, Takahashi M et al. (1996) Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. Nat Med 2:800–803PubMed
5.
Mohamed-Ali V, Goodrick S, Rawesh A et al. (1997) Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocr Metab 82:4196–4200PubMed
6.
Bastard JP, Jardel C, Bruckert E et al. (2000) Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 85:3338–3342
7.
Maffei M, Halaas J, Ravussin E et al. (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1:1155–1161
8.
Considine RV, Sinha MK, Heiman ML et al. (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295PubMed
9.
Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB (1995) The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 95:2111–2119PubMed
10.
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-a in human obesity and insulin resistance. J Clin Invest 95:2409–2415PubMed
11.
Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T (1998) Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 83:2907–2910PubMed
12.
Cella F, Adami GF, Giordano G, Cordera R (1999) Effects of dietary restriction on serum leptin concentration in obese women. Int J Obes Relat Metab Disord 23:494–497CrossRefPubMed
13.
Wadden TA, Considine RV, Foster GD, Anderson DA, Sarwer DB, Caro JS (1998) Short- and long-term changes in serum leptin dieting obese women: effects of caloric restriction and weight loss. J Clin Endocrinol Metab 83:214–218PubMed
14.
Kissebah AH, Vydelingum N, Murray R (1982) Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 54:254–260PubMed
15.
Hodge AM, Dowse GK, Zimmet PZ (1993) Association of body mass index and waist-hip circumference ratio with cardiovascular disease risk factors in Micronesian Nauruans. Int J Obes Relat Metab Disord 17:399–407PubMed
16.
Tokunaga K, Matsuzawa Y, Ishikawa K (1983) A novel technique for the determination of body fat by computed tomography. Int J Obes 7:437–745PubMed
17.
Suzuki R, Watanabe S, Hirai Y et al. (1993) Abdominal wall fat index, estimated by ultrasonography, for assessment of the ratio of visceral fat to subcutaneous fat in the abdomen. Am J Med 95:309–314PubMed
18.
Matsuzawa Y, Funahashi T, Nakamura T (2002) Molecular mechanism of vascular disease in metabolic syndrome X. J Diabetes Complications 16:17–18CrossRefPubMed
19.
Shibasaki M, Takahashi K, Itou T et al. (2002) Alterations of insulin sensitivity by the implantation of 3T3-L1 cells in nude mice. A role for TNF-alpha? Diabetologia 45:518–526CrossRef
20.
Neufeld, G, Cohen T, Gengrinovitch S, Poltrak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22PubMed
21.
Claffey KP, Wilkison WO, Spiegelman BM (1992) Vascular endothelial growth factor: regulation by cell differentiation and activated second messenger pathways. J Biol Chem 267:16317–16322PubMed
22.
Blann AD, Belgore FM, McCollum CN, Silverman S, Lip PL, Lip GY (2002) Vascular endothelial growth factor and its receptor, Flt-1, in the plasma of patients with coronary or peripheral atherosclerosis, or Type II diabetes. Clin Sci (Lond) 102:187–194
23.
Sato Y, Abe M, Tanaka K et al. (2000) Signal transduction and transcriptional regulation of angiogenesis. Adv Exp Med Biol 476:109–115PubMed
24.
Kobayashi J, Tashiro J, Murano S, Morisaki N, Saito Y. (1998) Lipoprotein lipase mass and activity in post-heparin plasma from subjects with intra-abdominal visceral fat accumulation. Clin Endocrinol 48:515–520CrossRef
25.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMed
26.
Emoto M, Nishizawa Y, Maekawa K et al. (1999) Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. Diabetes Care 22:818–822PubMed
27.
Bonora E, Targher G, Alberiche M et al. (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23:57–63PubMed
28.
Stephan CC, Brock TA (1996) Vascular endothelial growth factor, a multifunctional polypeptide. PR Health Sci J 15:169–178
29.
Ferrara N (2002) Links Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications. Semin Oncol 29:10–14
30.
Sreenath T, Matrisian LM, Stetler-Stevenson W, Gattoni-Celli S, Pozzatti RO (1992) Expression of matrix metalloproteinase genes in transformed rat cell lines of high and low metastatic potential. Cancer Res 52:4942–4947PubMed
31.
Kanaki T, Bujo H, Mori S et al. (2002) Functional analysis of aortic endothelial cells expressing mutant PDGF receptors with respect to expression of matrix metalloproteinase-3. Biochem Biophys Res Commun 2002 294:231–237CrossRef
Metadata
Title
Elevated serum vascular endothelial growth factor is associated with visceral fat accumulation in human obese subjects
Authors
S. Miyazawa-Hoshimoto
Dr. K. Takahashi
H. Bujo
N. Hashimoto
Y. Saito
Publication date
01-11-2003
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 11/2003
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-003-1221-6

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