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

Richardson, D.K., Jones, R.B. and Bailey, C.J. (2006). The primary amine metabolite of sibutramine stimulates lipolysis in adipocytes isolated from lean and obese mice and in isolated human adipocytes. Hormone and Metabolic Research, 38 (11), pp. 727-731.

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: Life & Health Sciences > Biosciences
Life & Health Sciences
Uncontrolled Keywords: β-adrenoceptors,lipolysis,M2,sibutramine,white adipose tissue,beta-adrenoceptors,Biochemistry,Endocrinology
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. ( 0000-0002-6998-6811)

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