Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes in primary culture via beta1- and beta2-adrenergic receptors

Abstract

Objective: Circulating leptin, the product of the ob gene, is known to be closely correlated with adipose tissue mass, but it is also subject to short-term regulation by a variety of hormones including catecholamines. The aim of this study was to investigate the contribution of the three b-adrenergic receptors to leptin secretion from cultured human adipocytes. Design and methods: The model of in vitro differentiated human subcutaneous adipocytes was used in this study. The presence of the b-adrenoceptor subtypes was studied by RT-PCR. The functional role of the receptor subtypes was determined by stimulation of lipolysis by selective b-adrenergic agonists and by measuring glycerol release. Leptin secretion into the medium of cultured human adipocytes from young normal-weight females was measured by radioimmunoassay. Results and conclusion: In a ®rst set of experiments, the expression of the three b-adrenergic receptor subtypes in cultured human adipocytes was demonstrated. To test their functional activity, the effect of the b-adrenoceptor agonists isoproterenol (non-selective agonist), dobutamine (b 1 -selective), fenoterol (b 2 -selective) and the b 3 -selective agonists BRL 37344 and CGP 12177 was studied. All agonists exhibited a dose-and time-dependent stimulation of glycerol release into the medium in a rather uniform manner. Isoproterenol rapidly reduced leptin secretion from cultured subcutaneous adipocytes in a dose-dependent fashion. Incubation with 10 À6 mol/l isoproterenol for 24 h resulted in a reduction of the leptin concentration by 48% (P < 0.01). A similar, but less pronounced suppressing effect was seen for dobutamine and fenoterol, whereas both BRL 37344 and CGP 12177 were not effective. These data provide evidence that catecholamines are able to suppress leptin release from differentiated human adipocytes, supporting the concept that leptin secretion is acutely regulated by surrounding hormones. This inhibition is obviously mediated via b 1 -and b 2 -adrenergic receptors.

Lipopolysaccharide-induced leptin release is neurally controlled

“…However, in the presence of LPS, propranolol slightly but not significantly decreased LPS-induced leptin release, suggesting that the inhibitory ␤ tone under resting conditions was not present after injection of LPS. Therefore, our data suggest that either circulating epinephrine and͞or norepinephrine or norepinephrine released from noradrenergic terminals may inhibit leptin release by acting on ␤-adrenergic receptors present on cell membranes of the adipocytes (28).…”

In situ lipolytic regulation in subjects born small for gestational age

“…Finally, it has been shown that catecholamines suppress leptin release via b1 and b2 adrenoreceptors. 32,33 Considering the increased lipolysis responsiveness to catecholamines, it cannot be ruled out that a comparable hypersensitivity to catecholamines-induced inhibition of leptin might explain, at least in part, the lower levels of serum leptin concentrations previously observed in subjects born SGA, which in turn might be regarded as an additional deleterious component in the control of insulin sensitivity. 26 Studying the lipolytic response to catecholamines in clearly insulin-resistant subjects born SGA in comparison to insulin-sensitive ones would certainly help to clarify the relationship between these two metabolic abnormalities in this specific clinical situation.…”

Plasma leptin and ghrelin in the neonatal rat: interaction of dexamethasone and hypoxia

“…Interestingly, concomitant hypoxia attenuated the stimulatory effect of dexamethasone on leptin. A previous study suggested that catecholamines directly inhibit leptin production by binding to adipocyte adrenergic receptors (Scriba et al 2000). It is possible that increased SNS activity in the hypoxic pup blunted the leptin response to dexamethasone.…”