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Effects of the two β3-agonists, ZD7114 and ZD2079 on 24 hour energy expenditure and respiratory quotient in obese subjects

International Journal of Obesity volume 24, pages 1553–1560 (2000)Cite this article

Abstract

OBJECTIVE: To analyze the effect of two different β3-adrenoceptor agonists, ZD7114 and ZD2079 on 24 h energy expenditure (EE) and substrate oxidations in obese weight-stable subjects.

DESIGN: Measurements of 24 h EE in a respiration chamber, before and after 14 days of treatment with one of the two β3-agonists or placebo during weight maintenance.

SUBJECTS: ZD7114 study: 7 male and 15 female subjects, body mass index (BMI) 28–39 kg/m2, age 27–64 y; ZD2079 study: 10 male and 7 female subjects, BMI 27–39 kg/m2, age 31–60 y.

MEASUREMENTS: EE was measured by indirect calorimetry, spontaneous physical activity (SPA) assessed by microwave radar, and 24 h heart rate was registered by telemetry. Serum potassium was measured to test for possible β2-adrenoceptor activity.

RESULTS: No effects of ZD7114 were found on tested parameters whereas there was a trend for a stimulatory effect of ZD2079 on 24 h EE (day 14-pretreatment; ZD2079 vs placebo: 0.4±1.1 vs −2.0±0.4%, P=0.06) and on SPA (day 14-pretreatment; ZD2079 vs placebo: 3.4±4.5 vs −7.7±2.7%, P=0.05). However, average 24 h heart rate decreased from 77.5±3.2 to 73.8±2.6 min−1 from pre-treatment to day 14 with placebo but remained the same with ZD2079 (P=0.03). The latter suggests some β1-adrenoceptor activity of the compound.

CONCLUSION: The lack of thermogenic response with ZD7114 and the very small and questionable response with ZD2079 probably demonstrate a lack of consistency between species in the responsiveness to β3-stimulation or a diversity in structure of the β3 receptor since both compounds have proven markedly selective thermogenic β3-properties in rodents.

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Acknowledgements

We thank the staff of the metabolic unit of the Research Department of Human Nutrition: Lis Kristoffersen, Tina Cuthbertson, Charlotte Nielsen, Inge Timmermann, Bente Knap, Bente Mathiasen and Inger-Lise Grønfeldt. The study was supported by ICI Pharmaceuticals later changed to Astra-Zeneca, Cheshire, UK, The Danish Research and Development Programme for Food Technology 1990-1994 and Danish Medical Research Council (grant 12-9537).

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  1. Research Department of Human Nutrition, The Royal Veterinary and Agricultural University, Copenhagen, Denmark

    B Buemann, S Toubro & A Astrup

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Correspondence to B Buemann.

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Buemann, B., Toubro, S. & Astrup, A. Effects of the two β3-agonists, ZD7114 and ZD2079 on 24 hour energy expenditure and respiratory quotient in obese subjects. Int J Obes 24, 1553–1560 (2000). https://doi.org/10.1038/sj.ijo.0801452

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