title: The amine oxidase inhibitor phenelzine limits lipogenesis in adipocytes without inhibiting insulin action on glucose uptake.
abstract: The antidepressant phenelzine is a monoamine oxidase inhibitor known to inhibit various other enzymes, among them semicarbazide-sensitive amine oxidase (currently named primary amine oxidase: SSAO/PrAO), absent from neurones but abundant in adipocytes. It has been reported that phenelzine inhibits adipocyte differentiation of cultured preadipocytes. To further explore the involved mechanisms, our aim was to study in vitro the acute effects of phenelzine on de novo lipogenesis in mature fat cells. Therefore, glucose uptake and incorporation into lipid were measured in mouse adipocytes in response to phenelzine, other hydrazine-based SSAO/PrAO-inhibitors, and reference agents. None of the inhibitors was able to impair the sevenfold activation of 2-deoxyglucose uptake induced by insulin. Phenelzine did not hamper the effect of lower doses of insulin. However, insulin-stimulated glucose incorporation into lipids was dose-dependently inhibited by phenelzine and pentamidine, but not by semicarbazide or BTT2052. In contrast, all these SSAO/PrAO inhibitors abolished the transport and lipogenesis stimulation induced by benzylamine. These data indicate that phenelzine does not inhibit glucose transport, the first step of lipogenesis, but inhibits at 100 μM the intracellular triacylglycerol assembly, consistently with its long-term anti-adipogenic effect and such rapid action was not found with all the hydrazine derivatives tested. Therefore, the alterations of body weight control consecutive to the use of this antidepressant drug might be not only related to central effects on food intake/energy expenditure, but could also depend on its direct action in adipocytes. Nonetheless, phenelzine antilipogenic action is not merely dependent on SSAO/PrAO inhibition.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U 1048 Bat L4, team 3, CHU Rangueil, Toulouse, France. christian.carpene@inserm.fr
authors.forename: Christian
authors.initials: C
authors.lastname: Carpéné
authors.forename: Sandra
authors.initials: S
authors.lastname: Grès
authors.forename: Simon
authors.initials: S
authors.lastname: Rascalou
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000502:physiology; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D050155:Lipogenesis / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010624:Phenelzine / Q000494:pharmacology*
chemical_list: D007328:Insulin; D008996:Monoamine Oxidase Inhibitors; D006631:Amine Oxidase (Copper-Containing); D005947:Glucose; D010624:Phenelzine