Horm Metab Res 2006; 38(11): 727-731
DOI: 10.1055/s-2006-955083
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

The Primary Amine Metabolite of Sibutramine Stimulates Lipolysis in Adipocytes Isolated from Lean and Obese Mice and in Isolated Human Adipocytes

D. K. Richardson 1 , R. B. Jones 2 , C. J. Bailey 3
  • 1Division of Diabetes, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, USA
  • 2Knoll Ltd. Research and Development, Nottingham, UK
  • 3School of Life and Health Sciences, Aston University, Birmingham, UK
Further Information

Publication History

Received 27 March 2006

Accepted after revision 27 June 2006

Publication Date:
16 November 2006 (online)

Abstract

Sibutramine is a satiety-inducing serotonin-noradrenaline reuptake inhibitor that acts predominantly via its primary and secondary metabolites. This study investigates the possibility that sibutramine and/or its metabolites could act directly on white adipose tissue to increase lipolysis. Adipocytes were isolated by a collagenase digestion procedure from homozygous lean (+/+) and obese-diabetic ob/ob mice, and from lean nondiabetic human subjects. The lipolytic activity of adipocyte preparations was measured by the determination of glycerol release over a 2-hour incubation period. The primary amine metabolite of sibutramine M2, caused a concentration-dependent stimulation of glycerol release by murine lean and obese adipocytes (maximum increase by 157±22 and 245±16%, respectively, p<0.05). Neither sibutramine nor its secondary amine metabolite M1 had any effect on lipolytic activity. Preliminary studies indicated that M2-induced lipolysis was mediated via a beta-adrenergic action. The non-selective beta-adrenoceptor antagonist propranolol (10-6 M) strongly inhibited M2-stimulated lipolysis in lean and obese murine adipocytes. M2 similarly increased lipolysis by isolated human omental and subcutaneous adipocytes (maximum increase by 194±33 and 136±4%, respectively, p<0.05) with EC50 values of 12 nM and 3 nM, respectively. These results indicate that the sibutramine metabolite M2 can act directly on murine and human adipose tissue to increase lipolysis via a pathway involving beta-adrenoceptors.

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Correspondence

Dawn K. RichardsonPh.D. 

Division of Diabetes MC 7886·Department of Medicine·The University of Texas Health Science Center at San Antonio

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Email: richardsond2@uthscsa.edu