Immunohistochemical identification of the β3-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine
Abstract
Objectives To investigate whether the beta(3)-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 beta(3)-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 beta(3)-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 beta(3)-adrenoceptor. The presence of the beta(3)-adrenoceptor in human white adipocytes is consistent with evidence that it can mediate lipolysis in human white adipocytes. The increased expression of the beta(3)-adrenoceptor in obese subjects treated with caffeine and ephedrine supports the potential of beta(3)-adrenoceptor agonists in the treatment of obesity and type 2 diabetes. Its expression in ventricular myocardium is consistent with evidence that the beta(3)-adrenoceptor mediates a negative inotropic effect in this tissue.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The combination of ephedrine and caffeine is a potent mediator of short-term weight loss that likely involves activation of BAT by β3 adrenergic receptors.
“However, the combination of ephedrine and caffeine is a potent mediator of short-term weight loss 139 that likely involves activation of BAT by β3 adrenergic receptors 140.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [140]
Cites
Hsu, S. M., Raine, L., & Fanger, H. (1981) · Journal of Histochemistry & Cytochemistry · doi:10.1177/29.4.6166661 · Cited by 14,248 · see citing works
Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes
Himms-Hagen, J., Melnyk, A., Zingaretti, M. C., Ceresi, E., Barbatelli, G., & Cinti, S. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.279.3.c670 · Cited by 593 · see citing works
Self-citationTissue distribution of beta 3-adrenergic receptor mRNA in man
Krief, S., Lönnqvist, F., Raimbault, S., Baude, B., Van Spronsen, A., Arner, P., Strosberg, A. D., Ricquier, D., & Emorine, L. J. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116191 · Cited by 528 · see citing works
Functional beta3-adrenoceptor in the human heart.
Gauthier, C., Tavernier, G., Charpentier, F., Langin, D., & Marec, H. L. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118823 · Cited by 461 · see citing works
Johnson, M. W. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.158.supplement_2.13tac110 · Cited by 396 · see citing works
Moniotte, S., Kobzik, L., Féron, O., Trochu, J., Gauthier, C., & Balligand, J. (2001) · Circulation · doi:10.1161/01.cir.103.12.1649 · Cited by 325 · see citing works
Brown adipose tissue thermogenesis and obesity
Himms‐Hagen, J. (1989) · Progress in Lipid Research · doi:10.1016/0163-7827(89)90009-x · Cited by 324 · see citing works
Igawa, Y., Yamazaki, Y., Takeda, H., et al. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702358 · Cited by 230 · see citing works
Takeda, M., Obara, K., Mizusawa, T., et al. (1999) · PubMed · Cited by 204 · see citing works
β3-Adrenoceptors in the cardiovascular system
Gauthier, C., Langin, D., & Balligand, J. (2000) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01562-5 · Cited by 187 · see citing works
EXPRESSION AND POSSIBLE FUNCTIONAL ROLE OF THE beta 3-ADRENOCEPTOR IN HUMAN AND RAT DETRUSOR MUSCLE
FUJIMURA, T., Tamura, K., TSUTSUMI, T., et al. (1999) · The Journal of Urology · doi:10.1016/s0022-5347(01)61994-3 · Cited by 162 · see citing works
Distribution of β3-adrenoceptor mRNA in human tissues
Berkowitz, D. E., Nardone, N. A., Smiley, R. M., Price, D. T., Kreutter, D. K., Fremeau, R. T., & Schwinn, D. A. (1995) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(95)90098-5 · Cited by 153 · see citing works
Physiology and Pathophysiology of Temperature Regulation
Blatteis, C. M. (1998) · WORLD SCIENTIFIC eBooks · doi:10.1142/3507 · Cited by 132 · see citing works
Chamberlain, P., Jennings, K., Paul, F., Cordell, J., Berry, A., Holmes, S., Park, J., Chambers, J., Sennitt, M. V., Stock, M. J., et al. (1999) · International Journal of Obesity · doi:10.1038/sj.ijo.0801039 · Cited by 127 · see citing works
Self-citationKaumann, A. J., Engelhardt, S. H., Hein, L., Molenaar, P., & Lohse, M. J. (2001) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s002100000336 · Cited by 116 · see citing works
Characterization of the human beta 3-adrenergic receptor gene.
Granneman, J. G., Lahners, K. N., & Chaudhry, A. (1993) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13147-7 · Cited by 113 · see citing works
Expression of beta3-adrenoceptors with low lipolytic action in human subcutaneous white adipocytes.
Tavernier, G., Barbe, P., Galitzky, J., Berlan, M., Caput, D., Lafontan, M., & Langin, D. (1996) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37638-0 · Cited by 96 · see citing works
Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block.
Granneman, J. G., Lahners, K. N., & Rao, D. D. (1992) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09278-8 · Cited by 93 · see citing works
Konkar, A. A., Zhai, Y., & Granneman, J. G. (2000) · PubMed · Cited by 92 · see citing works
Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans.
Liu, Y., Toubro, S., Astrup, A. V., & Stock, M. J. (1995) · PubMed · Cited by 89 · see citing works
Self-citationEnhanced thermogenic responsiveness during chronic ephedrine treatment in man
Astrup, A. V., Lundsgaard, C. C., Madsen, J., & CHRISTENSEN, N. J. (1985) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/42.1.83 · Cited by 89 · see citing works
Challiss, R. A. J., Leighton, B., Wllson, S., et al. (1988) · Biochemical Pharmacology · doi:10.1016/0006-2952(88)90186-4 · Cited by 83 · see citing works
Konkar, A. A., Zhu, Z., & Granneman, J. G. (2000) · PubMed · Cited by 73 · see citing works
Deng, C., Paoloni‐Giacobino, A., Kuehne, F., Boss, O., Revelli, J., Moinat, M., Cawthorne, M. A., Muzzin, P., & Giacobino, J. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15488.x · Cited by 64 · see citing works
Treatment of obesity with thermogenic beta-adrenoceptor agonists: studies on BRL 26830A in rodents.
Arch, J. R. S., Ainsworth, A. T., Ellis, R. D., Piercy, V., Thody, V. E., Thurlby, P. L., Wilson, C., Wilson, S., & Young, P. (1984) · PubMed · Cited by 63 · see citing works
Self-citationSennitt, M. V., Kaumann, A. J., Molenaar, P., Beeley, L. J., Young, P. W., Kelly, J., Chapman, H., Henson, S. M., Berge, J. M., Dean, D. K., et al. (1998) · PubMed · Cited by 59 · see citing works
Self-citationThomas, R. F., & Liggett, S. B. (1993) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13619-5 · Cited by 58 · see citing works
Influence of diet on de novo lipogenesis in artificially-fed 15- and 20-day-old Zucker fatty rats.
Thenen, S. W., Vy, G., Ta, P., & Grundleger, M. L. (1984) · PubMed · Cited by 55 · see citing works
Anthony, A., Schepelmann, Guillaume, et al. (1998) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.1998.00345.x · Cited by 54 · see citing works
Morphologic Techniques for the Study of Brown
Cinti, S., Zingaretti, M. C., Cancello, R., Ceresi, E., & Ferrara, P. (2003) · Humana Press eBooks · doi:10.1385/1-59259-231-7:021 · Cited by 46 · see citing works
Self-citationThurlby, P. L., & Ellis, R. D. M. (1986) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y86-189 · Cited by 45 · see citing works
Casteilla, L., Muzzin, P., Revelli, J. P., et al. (1994) · Biochemical Journal · doi:10.1042/bj2970093 · Cited by 40 · see citing works
Ito, M., Grujić, D., Abel, E. D., et al. (1998) · Diabetes · doi:10.2337/diabetes.47.9.1464 · Cited by 39 · see citing works
The β3-Adrenergic System and β3-Adrenergic Agonists
Arch, J. R. S. (2001) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1011852500209 · Cited by 23 · see citing works
Self-citationSkeletal muscle beta-adrenoceptor distribution and responses to isoproterenol in hyperthyroidism
Martin, W. H., Korte, E., Tolley, T., et al. (1992) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1992.262.4.e504 · Cited by 21 · see citing works
(2000) · CRC Press eBooks · doi:10.1201/b15045 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cellular bioenergetics as a target for obesity therapy
Tseng, Y.-H., Cypess, A. M., & Kahn, C. R. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3138 · Cited by 591 · see citing works
Transdifferentiation properties of adipocytes in the adipose organ
Cinti, S. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00183.2009 · Cited by 379 · see citing works
Self-citationLiu, T., Ji, R.-L., & Tao, Y.-X. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108044 · Cited by 34 · see citing works
- Authors
- De Matteis, R., Arch, J., Petroni, M., Ferrari, D., Cinti, S., & Stock, M.
- Affiliations
- IRCCS Istituto Auxologico Italiano (IT)
- University of Buckingham (GB)
- St George's, University of London (GB)
- Corresponding author
- Cinti, S
- ORCID
- Cinti, S
- Venue
- International Journal of Obesity
- Published
- 2002-11
- Volume
- 26
- Issue
- 11
- Pages
- 1442-1450
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2063854776
- Cited by
- 85
- References
- 36
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 1 · 2019: 8 · 2018: 5 · 2016: 8 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 4
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- beta3-adrenergic receptor, white adipocytes, brown adipocytes, obesity, ephedrine, caffeine, lipolysis, ventricular myocardium, receptor subcellular distribution, pheochromocytoma, type 2 diabetes, negative inotropic effect, hypocaloric diet
- MeSH terms
- Adipose Tissue, Adolescent, Adrenergic beta-Agonists, Adult, Caffeine, Ephedrine, Female, Heart Ventricles, Humans, Immunohistochemistry, Male, Myocardium, Obesity, Morbid, Adipocytes, Receptors, Adrenergic, beta-3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review