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Glitazones inhibit human monoamine oxidase but their anti-inflammatory actions are not mediated by VAP-1/semicarbazide-sensitive amine oxidase inhibition

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Abstract

Glitazones are peroxisome proliferator-activated receptor gamma (PPARγ) agonists widely used as antidiabetic drugs also known as thiazolidinediones. Most of them exert other effects such as anti-inflammatory actions via mechanisms supposed to be independent from PPARγ activation (e.g., decreased plasma monocyte chemoattractant protein-1 (MCP-1) levels). Recently, pioglitazone has been shown to inhibit the B form of monoamine oxidase (MAO) in mouse, while rosiglitazone and troglitazone were described as non-covalent inhibitors of both human MAO A and MAO B. Since molecules interacting with MAO might also inhibit semicarbazide-sensitive amine oxidase (SSAO), known as vascular adhesion protein-1 (VAP-1), and since VAP-1/SSAO inhibitors exhibit anti-inflammatory activity, our aim was to elucidate whether VAP-1/SSAO inhibition could be a mechanism involved in the anti-inflammatory behaviour of glitazones. To this aim, MAO and SSAO activities were measured in human subcutaneous adipose tissue biopsies obtained from overweight women undergoing plastic surgery. The production of hydrogen peroxide, an end-product of amine oxidase activity, was determined in tissue homogenates using a fluorometric method. The oxidation of 1 mM tyramine was inhibited by pargyline and almost resistant to semicarbazide, therefore predominantly MAO-dependent. Rosiglitazone was more potent than pioglitazone in inhibiting tyramine oxidation. By contrast, benzylamine oxidation was only abolished by semicarbazide: hence SSAO-mediated. Pioglitazone hampered SSAO activity only when tested at 1 mM while rosiglitazone was inefficient. However, rosiglitazone exhibited anti-inflammatory activity in human adipocytes by limiting MCP-1 expression. Our observations rule out any involvement of VAP-1/SSAO inhibition and subsequent limitation of leukocyte extravasation in the anti-inflammatory action of glitazones.

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Acknowledgments

The authors express gratitude to Philippe Valet and Michel Berlan (Univ. Paul Sabatier, Toulouse, France) for their knowledge on human adipocyte biology, and to their colleagues for their help with biochemical analyses. We would like to thank the staff of Plastic Surgery Dpt. of Rangueil Hospital (Toulouse, France) for facilitating access to post-surgical wastes.

Conflicts of interest

The authors have no conflicts of interest to disclose in the field of this work.

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Authors and Affiliations

  1. Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale (INSERM U1048), Toulouse, France

    Christian Carpéné, Mathilde Bizou, Karine Tréguer, Mounia Hasnaoui & Sandra Grès

  2. Université Paul Sabatier, I2MC-UPS, Hôpital Rangueil, Batiment L4, 31432, Toulouse Cedex 4, France

    Christian Carpéné, Mathilde Bizou, Karine Tréguer, Mounia Hasnaoui & Sandra Grès

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Correspondence to Christian Carpéné.

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Carpéné, C., Bizou, M., Tréguer, K. et al. Glitazones inhibit human monoamine oxidase but their anti-inflammatory actions are not mediated by VAP-1/semicarbazide-sensitive amine oxidase inhibition. J Physiol Biochem 71, 487–496 (2015). https://doi.org/10.1007/s13105-014-0379-3

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