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Immunohistochemical identification of the β3-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine

International Journal of Obesity volume 26, pages 1442–1450 (2002)Cite this article

Abstract

OBJECTIVES: To investigate whether the β3-adrenoceptor could be identified by immunohistochemistry in intact human white and brown adipocytes and other human tissues, and to investigate the influence of obesity and its treatment with ephedrine and caffeine on the expression of the β3-adrenoceptor in adipocytes.

METHODS: Morbidly obese patients were given a hypoenergetic diet (70% of energy expenditure) and some were also treated with ephedrine and caffeine (20/200 mg, three times daily) for 4 weeks. Adipose tissue and other tissues were taken during surgery. Immunohistochemistry was carried out using a monoclonal antibody raised against the human β3-adrenoceptor.

RESULTS: Staining was localized to the periphery of cells. All white adipocytes were stained. Those from lean subjects and obese subjects treated with ephedrine and caffeine showed more intense staining than those from untreated obese subjects. Staining was more intense in brown than in white adipocytes in perirenal adipose tissue from phaeochromocytoma patients. Staining was also seen in ventricular myocardium, and in smooth muscle of the prostate, ileum, colon and gall bladder.

DISCUSSION: The tissue and subcellular distribution of staining was consistent with it being due to binding of the antibody to the human β3-adrenoceptor. The presence of the β3-adrenoceptor in human white adipocytes is consistent with evidence that it can mediate lipolysis in human white adipocytes. The increased expression of the β3-adrenoceptor in obese subjects treated with caffeine and ephedrine supports the potential of β3-adrenoceptor agonists in the treatment of obesity and type 2 diabetes. Its expression in ventricular myocardium is consistent with evidence that the β3-adrenoceptor mediates a negative inotropic effect in this tissue.

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Acknowledgements

We wish to thank Dr Mauro Toppino for providing adipose tissue biopsies and Professor Franco Balzola, Dr Sebastiano Avagnina (Molinette Hospital, Turin) and Professor Francesco Cavagnini (Istituto Auxologico Italiano, Milano) for their valuable contribution to the clinical protocol in the obese patients; we thank Dr Michele Bisceglia (‘Casa Sollievo della Sofferenza’ Hospital, S. Giovanni Rotondo), Professor Aldo Bertani, Professor Aroldo Fianchini, Professor Edoardo Landi, Professor Cristina Marmorale, Professor Giovanni Muzzonigro (University Hospital, Ancona) for providing human tissue biopsies and Dr Claudia Venturini for her valuable help (Ancona University). This work was supported by grants from the Italian Ministry of Health (RF 1996) to Istituto Auxologico Italiano and from the Italian Ministery of University and Scientific Research (MIUR) and the University of Ancona to S Cinti.

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Author notes

  1. S Cinti

    Present address: Clore Laboratory, University of Buckingham, Buckingham, MK18 1EG, UK

  2. MJ Stock: Mike Stock died on 26 March 2001, a few weeks after drafting this manuscript. This paper is dedicated to his memory.

Authors and Affiliations

  1. Institute of Normal Human Morphology-Anatomy, University of Ancona, Ancona, Italy

    R De Matteis & S Cinti

  2. GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK

    JRS Arch

  3. Nutrition Research Laboratory, Istituto Auxologico Italiano, Verbania, Italy

    ML Petroni & D Ferrari

  4. Department of Physiology, St George's Hospital Medical School, London, UK

    MJ Stock

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Correspondence to S Cinti.

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De Matteis, R., Arch, J., Petroni, M. et al. Immunohistochemical identification of the β3-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine. Int J Obes 26, 1442–1450 (2002). https://doi.org/10.1038/sj.ijo.0802148

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