Abstract
Tyramine is found in foodstuffs, the richest being cheeses, sausages, and wines. Tyramine has been recognized to release catecholamines from nerve endings and to trigger hypertensive reaction. Thereby, tyramine-free diet is recommended for depressed patients treated with irreversible inhibitors of monoamine oxidases (MAO) to limit the risk of hypertension. Tyramine is a substrate of amine oxidases and also an agonist at trace amine-associated receptors. Our aim was to characterize the dose-dependent effects of tyramine on human adipocyte metabolic functions. Lipolytic activity was determined in adipocytes from human subcutaneous abdominal adipose tissue. Glycerol release was increased by a fourfold factor with classical lipolytic agents (1 μM isoprenaline, 1 mM isobutylmethylxanthine) while the amine was ineffective from 0.01 to 100 μM and hardly stimulatory at 1 mM. Tyramine exhibited a partial antilipolytic effect at 100 μM and 1 mM, which was similar to that of insulin but weaker than that obtained with agonists at purinergic A1 receptors, α2-adrenoceptors, or nicotinic acid receptors. Gi-protein blockade by Pertussis toxin abolished all these antilipolytic responses save that of tyramine. Indeed, tyramine antilipolytic effect was impaired by MAO-A inhibition. Tyramine inhibited protein tyrosine phosphatase activities in a manner sensitive to ascorbic acid and amine oxidase inhibitors. Thus, millimolar tyramine restrained lipolysis via the hydrogen peroxide it generates when oxidized by MAO. Since tyramine plasma levels have been reported to reach 0.2 μM after ingestion of 200 mg tyramine in healthy individuals, the direct effects we observed in vitro on adipocytes could be nutritionally relevant only when the MAO-dependent hepato-intestinal detoxifying system is overpassed.
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Acknowledgements
We would like to express our gratitude to the staff of Plastic Surgery Dpt. of Rangueil Hospital (Toulouse, France) for facilitating access to pieces of adipose tissue and to D. Prévot and S. Bour for their expertise in adipocyte management. The authors also acknowledge A. Bouloumié (I2MC, Toulouse) and M. Lafontan for facilitating scientific exchanges. In memory of J.C. Murat, our missing master who was a pioneer in the study of metabolic regulations.
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The experimental design was approved by local hospital under the agreement of INSERM guidelines (Institut National de la Santé et de la Recherche Médicale) and of the ethic committee for the protection of individuals under the reference DC-2008-452.
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Carpéné, C., Galitzky, J., Belles, C. et al. Mechanisms of the antilipolytic response of human adipocytes to tyramine, a trace amine present in food. J Physiol Biochem 74, 623–633 (2018). https://doi.org/10.1007/s13105-018-0643-z
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DOI: https://doi.org/10.1007/s13105-018-0643-z