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

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 mug/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 similar to 45% (P = 0.02). A corresponding local beta-adrenoceptor blockade with propranolol (10(-4) M), inhibited the increase in adipose glycerol levels by similar to 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.