Dr. Christian Carpéné, Principal Investigator

Contact e-mail: christian.carpene@inserm.fr

Background :

During the search for the function of the Imidazoline binding sites (I2) present in various tissues and only known to share some binding properties with alpha2-adrenoceptors, Christian Carpéné has reported for the first time that such sites were directly related with monoamine oxidases (MAO). In a pharmacological approach, he demonstrated that the I2 sites were abundant in adipose depots in rodents as well as in man. Other amine oxidases, sensitive to semicarbazide inhibition (SSAO), already known in other tissues to eliminate several biogenic amines and to generate H2O2, were also found to be highly expressed at the cell surface of adipocytes. Coworking with various european partners, Christian Carpéné has shown that numerous substrates of amine oxidases activate in vitro glucose utilisation in adipocytes and cardiomyocytes, via the hydrogen peroxide they produce during oxidative deamination. A novel role of MAO and SSAO was therefore proposed in the  regulation of fuel metabolism and on adipose tissue development. Later, Carpéné’s investigations brought the evidence that SSAO activity is increasing during adipocyte differentiation and that benzylamine and other SSAO substrates, can activate lipogenesis and inihbit lipolysis.

Moreover, several vascular endothelial cells express also SSAO at their surface which is also known as vascular adhesion protein (VAP-1) and which is implicated in leukocyte binding and extravasation. It was found that mice invalidated for the AOC3 gene, that  encodes for SSAO/VAP-1, exhibited a lower number of immune cells in their adipose depots than their wild type control. Since a low-grade inflammation of adipose tissue has been observed in obesity-associated disorders such as insulin-resistant states and metabolic syndrome, the  SSAO/VAP1 may constitute a still unexplored keystone in the deleterious complications of obesity. The ongoing researchs are thus aiming to further describe on animal models the SSAO regulation and the consequences of its blockade or its sustained activation on adipocyte biology, adipose  tissue physiology, especially in the case of  diabetes  and obesity.

He also manage the NET "Potential role of mediterranean diet components in the treatments of obesity, hyperlipidaemia and diabetes" designed to share expertise of research teams in Nutrition and Metabolism working on both sides of the Pyrenees. 

Selected publications:

1. Bour S., Caspar-Bauguil S., Iffiú-Soltész Z., Nibbelink M., Cousin B., Miiluniemi M., Salmi M., Stolen C., Jalkanen S., Casteilla L., Pénicaud L., Valet P. & Carpéné C. : Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition. Am. J. Pathol., 2009, 174, 1075-1083.
2. Carpéné C., Abello V., Iffiú-Soltész Z., Mercier N., Fève B. & Valet P. : Limitation of adipose tissue enlargement in rats chronically treated with semicarbazide-sensitive amine oxidase and monoamine oxidase inhibitors. Pharmacol. Res., 2008, 57, 426-434.
3. Prévot D., Soltesz Z., Abello V., Wanecq E., Valet P., Unzeta M. & Carpéné C. : Prolonged treatment with aminoguanidine strongly inhibits adipocyte semicarbazide-sensitive amine oxidase and slightly reduces fat deposition in obese Zucker rats. Pharmacol. Res., 2007, 56, 70-79.
4. Bour S., Daviaud D., Gres S., Lefort C., Prévot D., Zorzano A., Wabitsch M., Saulnier-Blache J-S., Valet P. & Carpéné C. : Adipogenesis-related increase of semicarbazide-sensitive amine oxidase and monoamine oxidase in human adipocytes. Biochimie, 2007, 89, 916-925.
5. Carpéné C., Daviaud D., Boucher J., Bour S., Visentin V., Grès S., Duffaut C., Fontana E., Testar X., Saulnier-Blache J-S. & Valet P. : Short- and long-term insulin-like effects of monoamine oxidase and semicarbazide-sensitive amine oxidase substrates in cultured adipocytes. Metabolism, 2006, 55, 1397-1405

Link: http://adipolab.weebly.com/