Abstract
Aims: This observational study aimed to investigate the effects of renin-angiotensin system (RAS) blockers on plasma adiponectin in subjects with metabolic syndrome (Mets) and differentiation, adiponectin expression of human omental (OM) and subcutaneous (SC) preadipocytes.
Methods: Fifty-three patients with Mets were treated with angiotensin converting enzyme inhibition (ACEI), angiotensin II receptor blocker (ARB) or nothing, lipid profile and adiponetin were measured. OM and SC preadipocytes were obtained from sixteen normal non-menopausal women undergoing elective abdominal surgery and subsequently differentiated in the presence of ACE, ARB or thiazolidinedione (TZD). Differentiation was assessed using a number of biochemical and function parameters.
Results: Plasma adiponectin was increased dramatically as a result of ACEI and ARB treatment. Most of the metabolic and differentiating parameters were improved significantly by RAS blockers or TZD. Compared with TZD, RAS blockers have stronger effects on omental preadipocytes in differentiation and insulin sensitivity. The improvement of adiponectin mRNA expression was significantly greater in ARB-treated omental preadipocytes compared with TZD-treated ones.
Conclusion: These results suggest that adiponectin may serve as potential therapeutic targets of ACEI and ARB for treating the Mets and its related complications. It also suggests a potential benefit of RAS blockers on Mets with characteristic visceral obesity.
Key words
renin-angiotensin system - preadipocytes - metabolic syndrome - cell differentiation - adiponectin
References
1
Adams M, Montague CT, Prins JB. et al .
Activator of peroxisome proliferators-activated receptor gamma have depot-sepcific effects on human preadipocyte differentiation.
J Clin Invest.
1997;
100
3149-3153
2
Arita Y, Kihara S, Ouchi N. et al .
Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.
Biochem Biophys Res Commun.
1999;
257
79-83
3
Bradford MM.
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
Anal Biochem.
1976;
72
248-254
4
Chin-Lin Hsu, Gow-Chin Yen.
Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells.
J Agric. Food Chem.
2007;
55
1730-1736
5
Clasen R, Schupp M, Foryst-Ludwig A.
PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin.
Hypertension.
2005;
46
137-143
6
Dahlöf B, Devereux RB, Kjeldsen SE. et al. .
Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol.
Lancet.
2002;
359
995-1003
7
Dai MH, Xia T, Zhang GD. et al .
Cloning, expression and chromosome localization of porcine adiponectin and adiponectin receptors genes.
Domest Anim Endocrinol.
2006;
30
117-125
8
Derosa G, Fogari E, D’Angelo A. et al .
Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone.
J Clin Pharm Ther.
2007;
32
261-268
9
Erbe DV, Gartrell K, Zhang YL. et al .
Molecular activation of PPARgamma by angiotensin II type 1-receptor antagonists.
Vascul Pharmacol.
2006;
45
154-162
10
Fain JN, Madan AK, Hiler ML. et al .
Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans.
Endocrinology.
2004;
145
2273-2282
11
Francke S, Manraj M, Lacquemant C. et al .
A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27.
Hum Mol Genet.
2001;
10
2751-2765
12
Furuhashi M, Ura N, Higashiura K. et al .
Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension.
Hypertension.
2003;
42
76-81
13
Giacchetti G, Faloia E, Mariniello B. et al .
Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects.
Hypertension.
2002;
15
381-388
14
Goossens GH, Blaak EE, van Baak MA.
Possible involvement of the adipose tissue renin-angiotensin system in the pathophysiology of obesity and obesity-related disorders.
Obes Rev.
2003;
4
43-55
15
Harmelen V, Elizalde M, Ariapart P. et al .
The association of human adipose angiotensinogen gene expression with abdominal fat distribution in obesity.
Int J Obes Relat Metab Disord.
2000;
24
673-678
16
Hattori Y, Akimoto K, Gross SS. et al .
Angiotensin-II-induced oxidative stress elicits hypoadiponectinaemia in rats.
Diabetologia.
2005;
48
1066-1074
17
Iwaki M, Matsuda M, Maeda N. et al .
Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors.
Diabetes.
2003;
52
1655-1663
18
Janke J, Engeli S, Gorzelniak K. et al .
Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors.
Diabetes.
2002;
51
1699-1707
19
Karagiannis A, Mikhailidis DP, Athyros VG. et al .
The role of renin-angiotensin system inhibition in the treatment of hypertension in metabolic syndrome: are all the angiotensin receptor blockers equal?.
Expert Opin Ther Targets.
2007;
11
191-205
20
Katsuki A, Suematsu M, Gabazza EC. et al .
Increased oxidative stress is associated with decreased circulating levels of adiponectin in Japanese metabolically obese, normal-weight men with normal glucose tolerance.
Diabetes Res Clin Prac.
2006;
73
310-314
21
Kim S, Soltani-Bejnood M, Quignard-Boulange A. et al .
The adipose Renin-Angiotensin System modulates systemic markers of insulin sensitivity and activates the intrarenal Renin-Angiotensin System.
J Biomed Biotechnol.
2006;
2006
1-6
22
Kurata A, Nishizawa H, Kihara S. et al .
Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation.
Kidney Int.
2006;
70
1717-1724
23
Lely AT, Krikken JA, Bakker SJ. et al .
Low dietary sodium and exogenous angiotensin II infusion decrease plasma adiponectin concentrations in healthy men.
J Clin Endocrinol Metab.
2007;
92
1821-1826
24
Lu YH, Lu JM, Wang SY. et al .
Comparison of the diagnostic criteria of metabolic syndrome by International Diabetes Federation and that by Chinese Medical Association Diabetes Branch.
Zhonghua Yi Xue Za Zhi.
2006;
86
386-389
25
Moriuchi A, Yamasaki H, Shimamura M. et al .
Induction of human adiponectin gene transcription by telmisartan, angiotensin receptor blocker, independently on PPAR-gamma activation.
Biochem Biophys Res Commun..
2007;
356
1024-1030
26
Mori Y, Itoh Y, Tajima N.
Angiotensin II receptor blockers downsize adipocytes in spontaneously type 2 diabetic rats with visceral fat obesity.
Am J Hypertens.
2007;
20
431-436
27
Negro R, Formoso G, Hassan H.
The effects of irbesartan and telmisartan on metabolic parameters and blood pressure in obese, insulin resistant, hypertensive patients.
J Endocrinol Invest.
2006;
29
957-961
28
Nishida M, Moriyama T, Sugita Y. et al .
Interleukin-10 associates with adiponectin predominantly in subjects with metabolic syndrome.
Circ J.
2007;
71
1234-1238
29
Nishizawa H, Shimomura I, Kishida K. et al .
Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein.
Diabetes.
2002;
51
2734-2741
30
Quinkler M, Bujalska IJ, Tomlinson JW. et al .
Depot-specific prostaglandin synthesis in human adipose tissue: a novel possible mechanism of adipogenesis.
Gene.
2006;
380
137-143
31
Rahmouni K, Mark AL, Haynes WG. et al .
Adipose depot-specific modulation of angiotensinogen gene expression in diet-induced obesity.
Am J Physiol Endocrinol Metab.
2004;
286
E891-E895
32
Schupp M, Janke J, Clasen R. et al .
Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity.
Circulation.
2004;
109
2054-2057
33
Sewter CP, Blows F, Vidal-Puig A. et al .
Regional differences in the response of human pre-adipocytes to PPARγ and RXRα agonists.
Diabetes.
2002;
51
718-723
34
Wang B, Jenkins JR, Trayhurn P.
Expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture: integrated response to TNF-alpha.
Am J Physiol Endocrinol Metab.
2005;
288
E731-E740
35
Zorad S, Dou JT, Benicky J. et al .
Long-term angiotensin II AT1 receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPARgamma.
Eur J Pharmacol.
2006;
552
112-122
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