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Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

International Journal of Obesity volume 32, pages 1201–1210 (2008)Cite this article

Abstract

Objective:

To characterize the interactive effects of amylin with phentermine or sibutramine on food intake, body weight/composition and gene expression in diet-induced obese (DIO) rats.

Design:

DIO rats were intraperitoneally injected with a single dose of amylin (10 μg kg−1) and/or phentermine (1 mg kg−1) or chronically infused with amylin (100 μg kg−1 d−1) or vehicle with or without phentermine (0.5–10 mg kg−1 d−1) or sibutramine (3 mg kg−1 d−1) using two surgically implanted subcutaneous osmotic mini-pumps.

Measurements:

Twenty-four hour food intake, locomotor activity and components of meal microstructure (meal size, latency, duration and intermeal interval) were measured following acute administration (amylin, phentermine or amylin+phentermine). Body weight and composition (for amylin and/or sibutramine or phentermine) and metabolism-related gene mRNA expression in the liver (fatty acid synthase, stearoyl-CoA desaturase-1 and carnitine palmitoyltransferase-1) and brown fat (β-adrenergic receptors and uncoupling protein-1) were measured (for amylin and/or phentermine) after sustained infusion (2 weeks).

Results:

Acute co-administration of amylin (10 μg kg−1) and phentermine (1 mg kg−1) reduced acute food intake (up to 19 h) more than either monotherapy. In two studies, sustained subcutaneous infusion of amylin for 2 weeks decreased cumulative food intake (22%) and vehicle-corrected body weight gain (∼4–8%). Phentermine's anorexigenic (10–17%) and weight-reducing effects (∼0–5%) were only evident at the highest dose tested (10 mg kg−1 d−1). Combination of amylin (100 μg kg−1 d−1) and phentermine reduced food intake (30–43%), body weight (8–12%) and adiposity to a greater extent than either monotherapy. Amylin prevented phentermine-induced reductions in UCP-1 mRNA in brown adipose tissue. When amylin+sibutramine were infused, mathematically additive decreases in food intake (up to 45%) and body weight (up to 12%) were evident. Similar to amylin+phentermine treatment, amylin+sibutramine mediated weight loss was attributable to significant reductions in fat mass.

Conclusions:

Combined treatment of DIO rats with the pancreatic β-cell hormone amylin and phentermine or sibutramine resulted in additive anorexigenic, weight- and fat-reducing effects.

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Acknowledgements

The manuscript was reviewed by all authors, who also contributed to and reviewed the final manuscript. We thank Heather Hughes for valuable technical assistance and Amy Halseth for critically reviewing the manuscript.

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Authors and Affiliations

  1. Amylin Pharmaceuticals, Inc., San Diego, CA, USA

    J D Roth, J L Trevaskis, J Wilson, C Lei, J Athanacio, C Mack, N C Kesty, T Coffey, C Weyer & D G Parkes

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  1. J D Roth
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Correspondence to J D Roth.

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Roth, J., Trevaskis, J., Wilson, J. et al. Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats. Int J Obes 32, 1201–1210 (2008). https://doi.org/10.1038/ijo.2008.91

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