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Systemic nicotine stimulates human adipose tissue lipolysis through local cholinergic and catecholaminergic receptors

Abstract

OBJECTIVE: To evaluate whether the lipolytic effects of systemic nicotine are not only attributed to indirect adrenergic mechanisms, but also to a direct action of nicotine on fat cells.

DESIGN: The effect of a systemic nicotine infusion (0.5 µg/kg/min for 30 min) on lipolysis in subcutaneous adipose tissue was investigated in situ in 11 non-obese, non-smoking, healthy male subjects under placebo-controlled conditions.

MEASUREMENTS: By using microdialysis probes the glycerol levels (lipolysis index) and blood flow were monitored locally in subcutaneous adipose tissue.

RESULTS: Plasma nicotine levels peaked (7.2 ng/ml) at the end of the infusion. Nicotine induced a mean (±s.e.) percentage peak increase in adrenaline and noradrenaline plasma levels of 213±30% (P<0.01) and 118±5% (P<0.05), respectively. Nicotine increased venous plasma glycerol levels by 144±9% (P<0.001), arterialized plasma glycerol levels by 148±12% (P<0.001) and adipose glycerol levels by 148±16% (P<0.001), but did not alter blood flow. By inducing a local cholinoceptor blockade with mecamylamine (10−5 M) via the microdialysis system, the increase in adipose glycerol levels was inhibited by 45% (P=0.02). A corresponding local beta-adrenoceptor blockade with propranolol (10−4 M), inhibited the increase in adipose glycerol levels by 60% (P=0.02). Infusion of saline (ie placebo) had no effect on the parameters mentioned above.

CONCLUSION: Systemically administered nicotine induces lipolysis, in part by activating the classical adrenergic mechanism (mediated by a nicotine-induced release of catecholamines stimulating beta-adrenoceptors), and in part by directly activating a nicotinic cholinergic lipolytic receptor located in adipose tissue.

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Acknowledgements

Dr Fredrik Kuylenstierna, Pharmacia AB, Sweden, is greatly acknowledged for the measurements of nicotine and cotinine levels. The excellent technical assistance of Britt Marie Leijonhufvud, Catharina Hertel and Elisabette Dugner is greatly appreciated. This study was supported by grants from the Swedish Medical Research Council, the Swedish Tobacco Group and Clas Groschinsky Foundation.

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Andersson, K., Arner, P. Systemic nicotine stimulates human adipose tissue lipolysis through local cholinergic and catecholaminergic receptors. Int J Obes 25, 1225–1232 (2001). https://doi.org/10.1038/sj.ijo.0801654

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