Abstract
Adipocytes produce the endothelial-cell specific molecule-1 (ESM-1), which inhibits
leukocyte adhesion and migration through the endothelium. This study investigates
ESM-1 expression and regulation in human adipose tissue. Subcutaneous abdominal
adipose tissue was obtained from seventy postmenopausal women. Fourteen women
subsequently underwent non-pharmacological weight reduction. In vitro experiments were performed on adipocytes isolated from human mammary adipose
tissue. We determined gene expression by TaqMan RT-PCR and measured ESM-1 levels
in serum and cell culture medium by ELISA. Mature adipocytes produced ESM-1. ESM-1 gene expression was higher in adipocytes than in preadipocytes. Cortisol inhibited
ESM-1 gene expression in preadipocytes. Insulin and cortisol inhibited adipocyte ESM-1
production in adipocytes. This inhibitory effect of insulin was attenuated by
insulin resistance, as ESM-1 gene expression in subcutaneous adipose tissue was increased in obese, hyperinsulinemic
women. In contrast, ESM-1 serum levels were reduced in obese women and inversely
correlated to C-reactive protein levels. Five percent weight loss did not
markedly change gene expression. Circulating ESM-1 levels increased significantly,
albeit modestly. ESM-1 is actively produced by adipocytes. However, since ESM-1
adipocyte gene expression and circulating plasma levels are not correlated, other
sources of ESM-1 may be more important. Circulating ESM-1 levels are reduced in
the overweight and obese, consistent with the notion that ESM-1 may play some
role in obesity-associated vascular disease.
Key words
ESM-1 - adipocytes - preadipocytes - adipogenesis - insulin resistance
References
1
Lyon C J, Law R E, Hsueh W A.
Minireview: adiposity, inflammation, and atherogenesis.
Endocrinology.
2003;
144
2195-2200
2
Rajala M W, Scherer P E.
Minireview: The adipocyte - at the crossroads of energy homeostasis, inflammation,
and atherosclerosis.
Endocrinology.
2003;
144
3765-3773
3
Wellner M, Herse F, Janke J, Gorzelniak K, Engeli S, Bechart D, Lasalle P, Luft F C,
Sharma A M.
Endothelial cell specific molecule-1 - a newly identified protein in adipocytes.
Horm Metab Res.
2003;
35
217-221
4
Bechard D, Scherpereel A, Hammad H, Gentina T, Tsicopoulos A, Aumercier M, Pestel J,
Dessaint J P, Tonnel A B, Lassalle P.
Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18
(LFA-1) and blocks binding to intercellular adhesion molecule-1.
J Immunol.
2001;
167
3099-3106
5
Lassalle P, Molet S, Janin A, Heyden J V, Tavernier J, Fiers W, Devos R, Tonnel A B.
ESM-1 is a novel human endothelial cell-specific molecule expressed in lung
and regulated by cytokines.
J Biol Chem .
1996;
271
20 458-20 464
6
Bechard D, Meignin V, Scherpereel A, Oudin S, Kervoaze G, Bertheau P, Janin A, Tonnel A,
Lassalle P.
Characterization of the secreted form of endothelial-cell-specific molecule
1 by specific monoclonal antibodies.
J Vasc Res.
2000;
37
417-425
7
Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I,
Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y.
Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice.
Circulation.
2002;
106
2767-2770
8
Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M,
Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y.
Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma
protein adiponectin.
Circulation.
1999;
100
2473-2476
9
Janke J, Engeli S, Gorzelniak K, Luft F C, Sharma A M.
Mature adipocytes inhibit in vitro differentiation of human preadipocytes via
angiotensin type 1 receptors.
Diabetes.
2002;
51
1699-1707
10
Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, Mohlig M, Pfeiffer A F,
Luft F C, Sharma A M.
Association between adiponectin and mediators of inflammation in obese women.
Diabetes.
2003;
52
942-947
11
Gorzelniak K, Janke J, Engeli S, Sharma A M.
Validation of endogenous controls for gene expression studies in human adipocytes
and preadipocytes.
Horm Metab Res.
2001;
33
625-627
12
Aitkenhead M, Wang S J, Nakatsu M N, Mestas J, Heard C, Hughes C C.
Identification of endothelial cell genes expressed in an in vitro model of angiogenesis:
induction of ESM-1, (beta)ig-h3, and NrCAM.
Microvasc Res.
2002;
63
159-171
13
Tsai J C, Zhang J, Minami T, Voland C, Zhao S, Yi X, Lassalle P, Oettgen P, Aird W C.
Cloning and characterization of the human lung endothelial-cell-specific molecule-1
promoter.
J Vasc Res.
2002;
39
148-159
14
Shimura H, Miyazaki A, Haraguchi K, Endo T, Onaya T.
Analysis of differentiation-induced expression mechanisms of thyrotropin receptor
gene in adipocytes.
Mol Endocrinol.
1998;
12
1473-1486
15
Tong Q, Dalgin G, Xu H, Ting C N, Leiden J M, Hotamisligil G S.
Function of GATA transcription factors in preadipocyte-adipocyte transition.
Science.
2000;
290
134-138
16
Ridker P M, Rifai N, Rose L, Buring J E, Cook N R.
Comparison of C-reactive protein and low-density lipoprotein cholesterol levels
in the prediction of first cardiovascular events.
N Engl J Med.
2002;
347
1557-1565
Jürgen Janke, Ph. D.
Franz-Volhard Klinik · Charité
Wiltberg Straße 50 · 13125 Berlin · Germany ·
Phone: +49 30 9417 2271
Fax: +49 30 9417 2206
Email: janke@fvk.charite-buch.de