Abstract
Tyramine is naturally occurring in foods. This biogenic amine is known to induce hypertension, especially when ingested by individuals treated by irreversible inhibitors of monoamine oxidases (MAO). However, in animals, tyramine is also an agonist for trace amine-associated receptors and substrate of semicarbazide-sensitive amine oxidases (SSAO). Though tyramine can alter aminergic transmission by various mechanisms, it was recently reported that prolonged tyramine supplementation does not deteriorate glucose tolerance and does not cause adverse cardiovascular effects in mice. Since previous studies have described insulin-like effects of tyramine in fat cells from diabetic rats, we have further tested tyramine in vitro and in vivo actions on fattening. To this aim, antilipolytic and lipogenic responses to insulin and tyramine were first compared in rat adipocytes while tyramine oxidation was compared in adipose and intestinal tissues. Then, effects of repeated intraperitoneal injections of tyramine (17 µmol/kg/day) on adiposity and on adipocyte functions were studied in young and mature rats. Millimolar doses of tyramine inhibited glycerol release by adipocytes with a maximal antilipolytic effect comparable to that of insulin. Repeated tyramine administration enhanced fat deposition in epididymal white adipose tissue, irrespective of the age of treated rats. This effect was not accompanied by desensitization to lipogenic activation by insulin, tyramine or hydrogen peroxide. Lastly, tyramine was more readily oxidized in adipose than in intestinal tissues when enzymatic activity was expressed per mg of protein. Moreoever, MAO mostly contributed to oxidative deamination in gut while SSAO was predominant in fat. Thus, both short-term and prolonged effects of tyramine were evidencing somewhat insulin-like actions in adipose tissue and led to reconsider the risk/benefit ratio of the dietary intake of this amine.
Highlights
Tyramine is a naturally occurring molecule belonging to the families of dietary amines and trace amines
This amine is a metabolite of the amino acid tyrosine and is mainly known to be involved in the “cheese effect”, i.e. a fatal hypertensive crisis induced by dietary amines in depressive patients treated with irreversible inhibitors of monoamine oxidase (MAO)
We have already reported that tyramine activates glucose uptake and inhibits lipolysis in rat adipocytes in a manner that is: maximal at 1 mM, dependent on amine oxidation by monoamine oxidases (MAO) and sensitive amine oxidases (SSAO) [14], mediated by subsequent hydrogen peroxide production and potentiated by vanadium [15]
Summary
Tyramine is a naturally occurring molecule belonging to the families of dietary amines and trace amines. The pressor response to tyramine is a widely accepted screening method for quantifying the potential hypertensive complications triggered by drugs suspected to inhibit monoamine oxidases or to alter catecholaminergic transmission [2] Such pressor test is based on the determination of the tyramine dose producing a ≥ 30 mm Hg increase in systolic blood pressure in subjects previously treated by studied agents or placebo [3,4,5,6], considering that MAO irreversible inhibitors dramatically reduce such required tyramine dose. Since tyramine is found at high concentrations in cheese, dry sausage, red wine, beer and various other food items [9,10], their dietary intake has been restricted to avoid fatal hypertensive crisis during the therapeutic use of MAO inhibitors. For unmedicated adults, ingestion of more than 200 or 800 mg of tyramine is needed to induce a modest rise in blood pressure (~30 mm Hg) [12]
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