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Angiotensin II stimulates and atrial natriuretic peptide inhibits human visceral adipocyte growth

International Journal of Obesity volume 32, pages 259–267 (2008)Cite this article

Abstract

Objective:

Cardiovascular peptides such as angiotensin II (Ang II) and atrial natriuretic peptide (ANP) have metabolic effects on adipose cells. These peptides might also regulate adipocyte proliferation and visceral adipose tissue (VAT) expansion. Well-differentiated and stabilized primary cultures of human visceral mature adipocytes (MA) and in vitro-differentiated preadipocytes (DPA) were used as a model to study regulation of VAT expansion.

Methods:

Adipocyte differentiation was evaluated by Oil Red O staining and antiperilipin antibodies. MA and DPA from intra- and retro-peritoneal depots were treated with increasing Ang II (with or without valsartan, a highly selective, competitive, ‘surmountable’ AT1 antagonist devoid of peroxisome proliferator-activated receptor γ agonistic activity) or ANP concentrations. Cell counts and bromodeoxyuridine incorporation were used to evaluate proliferation. Apoptosis was evaluated by Hoechst 33342 staining. 8-Bromo cyclic guanosine monophosphate (8Br-cGMP) was used to investigate ANP effects, and real-time PCR to evaluate Ang II and ANP receptors' expression.

Results:

Cell proliferation was progressively stimulated by increasing Ang II concentrations (starting at 10−11 M) and inhibited by ANP (already at 10−13 M) in both MA and DPA. Co-incubation with increasing Ang II concentrations and valsartan indicated that Ang II effects were AT1-mediated. Indeed, AT2 receptors were not expressed. Valsartan alone slightly inhibited basal proliferation indicating an autocrine/paracrine growth factor-like effect of endogenous, adipocyte-derived Ang II. 8Br-cGMP experiments indicated that the effects of ANP were mediated by the guanylyl cyclase type A receptor.

Conclusion:

A cell-culture model to study VAT growth showed stimulation by Ang II and inhibition by ANP at physiological concentrations. Because similar effects are likely to occur in vivo, Ang II and ANP might be important modulators of VAT expansion and associated metabolic and cardiovascular consequences.

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Acknowledgements

This study was supported by research grants from the Italian University and Research Ministry (MiUR) and the University of Ancona ‘Politecnica delle Marche’. We are indebted to Dr Liana Spazzafumo, from the Statistic and Biometry Center, Department of Gerontological Research, National Institute for Research and Care on Aging (INRCA), Ancona, Italy, for statistical advice and with Professor Saverio Cinti and Dr Maria Cristina Zingaretti, Institute of Normal Human Morphology, University of Ancona—‘Politecnica delle Marche’, Ancona, Italy, for the help in the immunohistochemistry procedures. We also thank Mr Giorgio Tesei and Mrs Leda Rinaldi, in the year of their retirement, for the technical support in this as well as in many other studies performed in the last 20 years.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Ancona—‘Politecnica delle Marche’, Ancona, Italy

    R Sarzani, P Marcucci, F Salvi, M Bordicchia, E Espinosa, L Mucci, B Lorenzetti, P Dessì-Fulgheri & A Rappelli

  2. Department of Urology, University of Ancona—‘Politecnica delle Marche’, Ancona, Italy

    D Minardi & G Muzzonigro

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  1. R Sarzani
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Correspondence to R Sarzani.

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Sarzani, R., Marcucci, P., Salvi, F. et al. Angiotensin II stimulates and atrial natriuretic peptide inhibits human visceral adipocyte growth. Int J Obes 32, 259–267 (2008). https://doi.org/10.1038/sj.ijo.0803724

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