The primary amine metabolite of sibutramine stimulates lipolysis in adipocytes isolated from lean and obese mice and in isolated human adipocytes

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 ± 1696, 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 (10-6M) 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. © Georg Thieme Verlag KG Stuttgart.

Publication DOI: https://doi.org/10.1055/s-2006-955083
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
Uncontrolled Keywords: β-adrenoceptors,lipolysis,M2,sibutramine,white adipose tissue,beta-adrenoceptors,Biochemistry,Endocrinology
Publication ISSN: 1439-4286
Full Text Link: https://www.thi ... 5/s-2006-955083
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2006-11
Authors: Richardson, D.K.
Jones, R.B.
Bailey, C.J. (ORCID Profile 0000-0002-6998-6811)

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