Download PDF
Horm Metab Res 2001; 33(12): 708-712
DOI: 10.1055/s-2001-19132
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Elevated AT1 Receptor Protein but Lower Angiotensin II-Binding in Adipose Tissue of Rats with Monosodium Glutamate-Induced Obesity

L'. Pintérová 1 , B. Železná 2 , M. Ficková 1 , L. Macho 1 , O. Križanová 3 , D. Ježová 1 , Š. Zórad 1
  • 1 Institute of Experimental Endocrinology, SAS, Bratislava, Slovak Republic
  • 2 Institute of Molecular Genetics, ASCR, Prague, Czech Republic
  • 3 Institute of Molecular Physiology and Genetics, Bratislava, Slovak Republic
Further Information

Publication History

Publication Date:
18 December 2001 (online)

Also available at
    Permissions and Reprints

Age-related hypertrophy of adipose tissue has been associated with a significant decrease in the number of angiotensin II receptors. The aim of this study was to investigate the characteristics of angiotensin II receptors in hypertrophic adipose tissue in animal obesity model using rats postnatally treated with monosodium glutamate. Angiotensin II is known to induce hypertrophy in several tissues of the cardiovascular system and might do the same in fat tissue. The expression and binding properties of angiotensin II AT1 receptors in epididymal fat tissue of adult rats were studied using membrane-binding, RT-PCR, and immunoblotting. The amount of AT1 receptor mRNA did not differ significantly between obese and control rats. Despite that glutamate-treated rats displayed approximately 4-times more AT1 receptor immunoreactive protein content in fat tissue cell membranes than the controls did. In contrast, binding experiments showed a significant (40.3 ± 6.2 %) decrease of 125I-Sar1-Ile8-angiotensin II-binding to fat tissue cell membranes in obese rats compared to controls. In conclusion, the present study provides evidence for the low binding properties associated with an accumulation of AT1 receptor protein in cell membranes of the fat tissue of rats with glutamate-induced obesity. Discrepancies among angiotensin II-binding, AT1 receptor protein, and AT1 receptor mRNA levels indicate a possible defect in the receptor protein, which remains to be identified. The results obtained support a role of angiotensin II and AT1 receptors in the pathogenesis of obesity.

Key words:

AT1 Receptor - Fat Tissue - MSG Rat

References

  • 1 Olney J W. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate.  Science. 1969;  164 719-721
    CrossrefPubMedGoogle Scholar
  • 2 Redding T W, Schally A V, Arimura A, Wakabayashi I. Effect of monosodium glutamate on some endocrine functions.  Neuroendocrinology. 1971;  8 245-255
    PubMedGoogle Scholar
  • 3 Nemeroff C B, Konkol R J, Bissette G, Youngblood W, Martin J B, Brazeau P, Rone M S, Prange A J Jr, Breese G R, Kizer J S. Analysis of the disruption in hypothalamic-pituitary regulation in rats treated neonatally with monosodium L-glutamate (MSG): Evidence for the involvement of tuberoinfundibular cholinergic and dopaminergic systems in neuroendocrine regulation.  Endocrinology. 1977;  101 613-622
    PubMedGoogle Scholar
  • 4 Skultetyova I, Kiss A, Jezova D. Neurotoxic lesions induced by monosodium glutamate result in increased adenopituitary proopiomelanocortin gene expression and decreased corticosterone clearance in rats.  Neuroendocrinology. 1998;  67 412-420
    CrossrefPubMedGoogle Scholar
  • 5 Zorad S, Macho L, Jezova D, Fickova M. Partial characterization of insulin resistance in adipose tissue of monosodium glutamate-induced obese rats.  Ann N Y Acad Sci. 1997;  827 541-545
    PubMedGoogle Scholar
  • 6 Dolnikoff M S, Kater C E, Egami M, de Andrade I S, Marmo M R. Neonatal treatment with monosodium glutamate increases plasma corticosterone in the rat.  Neuroendocrinology. 1988;  48 645-649
    PubMedGoogle Scholar
  • 7 Kubota A, Nakagawa Y, Igarashi Y. Studies of gene expression in liver of insulin-like growth factor (IGF)-I, IGF binding protein-3 and growth hormone (GH) receptor/GH binding protein in rats treated with monosodium glutamate.  Horm Metab Res. 1994;  26 497-503
    PubMedGoogle Scholar
  • 8 Macho L, Jezova D, Zorad S, Fickova M. Postnatal monosodium glutamate treatment results in attenuation of corticosterone metabolic rate in adult rats.  Endocrine Regulations. 1999;  33 61-67
    PubMedGoogle Scholar
  • 9 Macho L, Fickova M, Jezova D, Zorad S. Late effects of postnatal administration of monosodium glutamate on insulin action in adult rats.  Physiol Res. 2000;  49 (Suppl. 1) S79-S85
    PubMedGoogle Scholar
  • 10 Hollenberg C H. Perspectives in adipose tissue physiology.  Int J Obes. 1990;  14 (Suppl. 3) 135-152
    PubMedGoogle Scholar
  • 11 Kissebah A H, Krakower G R. Regional adiposity and morbidity.  Physiol Rev. 1994;  74 761-811
    PubMedGoogle Scholar
  • 12 Crandall D L, Herzlinger H E, Saunders B D, Kral J G. Developmental aspects of adipose tissue renin-angiotensin system: therapeutic implications.  Drug Development Res. 1994;  32 117-125
    PubMedGoogle Scholar
  • 13 Darimont C, Vassaux G, Ailhaud G, Negrel R. Differentiation of preadipose cells paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin II.  Endocrinology. 1994;  135 2030-2036
    CrossrefPubMedGoogle Scholar
  • 14 Wabitsch M, Heinze E, Debatin K-M, Blum W F. IGF-I and IGFBP-3 expression in cultured human preadipocytes and adipocytes.  Horm Metab Res. 2000;  32 555-559
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Engeli S, Gorzelniak K, Kreutz R, Runkel N, Distler A, Sharma A M. Co-expression of renin-angiotensin system genes in human adipose tissue.  J Hypertens. 1999;  17 555-560
    CrossrefPubMedGoogle Scholar
  • 16 Engeli S, Sharma A M. Role of adipose tissue for cardiovascular-renal regulation in health and disease.  Horm Metab Res. 2000;  32 485-499
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Pinterova L, Krizanova O, Zorad S. Rat epididymal fat tissue express all components of the renin-angiotensin system.  Gen Physiol Biophys. 2000;  19 329-334
    PubMedGoogle Scholar
  • 18 Adams F, Klaus S, Boschmann M. Metabolic and hemodynamic response to angiotensin II in rat adipose tissue.  Int J Obes Relat Metab Disord. 2000;  24 S74
    PubMedGoogle Scholar
  • 19 Frederich R C, Kahn B B, Peach M J, Flier J S. Tissue-specific nutritional regulation of angiotensinogen in adipose tissue.  Hypertension. 1992;  19 339-344
    PubMedGoogle Scholar
  • 20 Zorad S, Fickova M, Zelezna B, Macho L, Kral J G. The role of angiotensin II and its receptors in regulation of adipose tissue metabolism and cellularity.  Gen Physiol Biophys. 1995;  14 383-391
    PubMedGoogle Scholar
  • 21 Crandall D L, Herzlinger H E, Saunders B D, Zolotor R C, Feliciano L, Cervoni P. Identification and characterization of angiotensin II receptors in rat epididymal adipocyte membranes.  Metabolism. 1993;  42 511-515
    CrossrefPubMedGoogle Scholar
  • 22 Mallow H, Trindl A, Löffler G. Production of angiotensin II receptors type one (AT1) and type two (AT2) during the differentiation of 3T3-L1 preadipocytes.  Horm Metab Res. 2000;  32 500-503
    PubMedGoogle Scholar
  • 23 Tokarev D, Kristova V, Kriska M, Jezova D. Treatment of neonatal rats with monosodium glutamate attenuates the cardiovascular reactivity to phenylephrine and angiotensin II.  Physiol Res. 1997;  46 165-171
    PubMedGoogle Scholar
  • 24 Munson P J, Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems.  Anal Biochem. 1980;  107 220-239
    CrossrefPubMedGoogle Scholar
  • 25 Zelezna B, Richards E M, Tang W, Lu D, Sumners C, Raizada M K. Characterization of a polyclonal anti-peptide antibody to the angiotensin II type-1 (AT1) receptor.  Biochem Biophys Res Commun. 1992;  183 781-788
    CrossrefPubMedGoogle Scholar
  • 26 Chomczynski P, Sacchi N. Single step mehod of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.  Anal Biochem. 1987;  162 156-159
    PubMedGoogle Scholar
  • 27 Langlois D, Ouali R, Berthelon M C, Derrien A, Saez J M. Regulation by growth factors of angiotensin II type-1 receptor and the α-subunit of Gq and G11 in bovine adrenal cells.  Endocrinology. 1994;  135 480-483
    CrossrefPubMedGoogle Scholar
  • 28 Shelat S G, Flanagan-Cato L M, Fluharty S J. Glucocorticoid and mineralocorticoid regulation of angiotensin II type 1 receptor binding and inositol triphosphate formation in WB cells.  J Endocrinol. 1999;  162 381-391
    CrossrefPubMedGoogle Scholar
  • 29 Leri A, Liu Y, Wang X, Kajstura J, Malhotra A, Meggs L G, Anversa P. Overexpression of insulin-like growth factor-1 attenuates the myocyte renin-angiotensin system in transgenic mice.  Circ Res. 1999;  84 752-762
    PubMedGoogle Scholar
  • 30 Dell G C, Morley S D, Mullins J J, Williams B C, Walker S W. Multiple signal transduction system regulate angiotensin II type 1 (AT1) receptor mRNA expression in bovine adrenocortical cells.  Endocr Res. 1996;  22 363-368
    PubMedGoogle Scholar
  • 31 Wajchenberg B L. Subcutaneous and visceral adipose tissue: Their relation to the metabolic syndrome.  Endocr Rev. 2000;  21 697-738
    Google Scholar

Štefan Zórad

Institute of Experimental Endocrinology
Slovak Academy of Sciences

Vlarska 3
833 06 Bratislava
Slovak Republic


Phone: + 421 (2) 54 77-28 00

Fax: + 421 (2) 54 77-42 47

Email: ueenstef@savba.sk

      >