Endocrinometabolic disturbances of mice lacking SSAO/VAP-1 by Aoc3 gene deletion are mostly reproduced in mice expressing a vascular adhesion protein-1 (VAP-1) devoid of amine oxidase activity (SSAO)

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Jargaud, Valentin | Tercé, François | Collet, Xavier | Mauriège, Pascale | Bouloumie-Diehl, Anne | Jalkanen, S. | Stolen, Craig | Salmi, M.

Edité par CCSD -

International audience. Background: Vascular Adhesion Protein-1 (VAP-1) encoded by Aoc3 gene exhibits Semicarbazide-Sensitive Amine Oxidase activity (SSAO). VAP-1/SSAO is highly expressed in endothelial, smooth muscle and fat cells, while also found in blood. Its multifaceted role remains unclear, since it facilitates leucocyte adhesion, oxidizes endogenous or dietary amines, and generates hydrogen peroxide and aldehydes. Its involvement in immunity is now well described, leading to the development of VAP-1/SSAO inhibitors and antibodies as novel anti-inflammatory agents. However, the exploration of VAP-1/SSAO functions connected with metabolism regulation is still incomplete. Objectives: In an attempt to decipher the respective role of adhesion molecule and that of amine oxidase generating highly reactive products, we compared the phenotype of mice with total Aoc3 gene knock-out (AOC3KO) and of mice expressing a mutated VAP-1 lacking SSAO activity (knock-in line called AOC3KI).Methods: In an attempt to decipher the respective role of adhesion molecule and that of amine oxidase generating highly reactive products, we compared the phenotype of mice with total Aoc3 gene knock-out (AOC3KO) and of mice expressing a mutated VAP-1 lacking SSAO activity (knock-in line called AOC3KI).Results: In both lines, no tissue SSAO activity was found, while AOC3 mRNA was absent in adipose tissues (AT) of AOC3KO only. Although food consumption was unchanged, both genders of AOC3KO and AOC3KI were heavier and fatter than respective controls. Other common features were found in AT: loss of benzylamine insulin-like effect in adipocytes, unchanged insulin sensitivity and adiponectin expression, inflammatory marker down-regulation (CD45, IL 6). Glucose tolerance and liver mass remained unchanged, while circulating lipid profile was distinctly altered, with increased cholesterol in AOC3KO only. Conclusion: These results suggest that the lack of primary oxidase activity of mutated VAP-1/SSAO is sufficient to reproduce the changes in metabolic homeostasis observed in AOC3KO mice, save those related with cholesterol handling.Conflict of interests: Authors declare no conflicts of interest with this work.

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