title: Histamine oxidation in mouse adipose tissue is controlled by the AOC3 gene-encoded amine oxidase.
abstract: BACKGROUND
  Histaminergic status can modify adipose tissue (AT) development: histamine-free mice exhibit visceral obesity, and treatments with H3-antagonists reduce body weight gain. However, direct histamine effects on AT remain poorly documented: it has been observed that histamine stimulates lipolysis in rodent adipocytes when its oxidation by amine oxidases (AOs) is blocked by inhibitors such as semicarbazide.
  
  
  OBJECTIVE
  The aim of this work was to study the influence of AOC3 gene invalidation, encoding for semicarbazide-sensitive AO (SSAO), on histamine oxidation and on histamine lipolytic activity in AT.
  
  
  METHODS
  Expression of AOC- and MAO-encoding genes was determined by real-type PCR in wild-type (WT) and SSAO-deficient (AOC3-KO) mice. Lipolysis was assessed by glycerol release in isolated adipocytes and AO activity by substrate-induced hydrogen peroxide formation in kidney, ileum and AT.
  
  
  RESULTS
  The expression levels of the genes encoding AOC1, AOC2 or MAOA and MAOB were not modified in the AT of AOC3-KO mice. In WT mice, histamine oxidation was lower than that of the reference SSAO-substrate benzylamine in AT, but not in ileum. The order of magnitude regarding benzylamine oxidation was AT > ileum >> kidney. In AOC3-KO mice, benzylamine oxidation was abolished in all tissues, while histamine oxidation was abolished in AT but not in ileum. Histamine was inactive on lipolysis in WT but stimulated lipolysis in fat cells from AOC3-KO mice, without reaching the maximal intensity of beta-adrenergic stimulation.
  
  
  CONCLUSIONS
  Histamine was mainly oxidized by diamine oxidase (AOC1 product) in intestine, but by SSAO (AOC3 product) in AT. When protected from its oxidation by SSAO in AT, histamine moderately activated lipolysis in adipocytes in AOC3-KO mice.
authors.affiliation: INSERM U858, IFR 150, I2MR, Université Toulouse III Paul-Sabatier, CHU Rangueil, Toulouse, France.
authors.forename: Z
authors.initials: Z
authors.lastname: Iffiú-Soltész
authors.forename: E
authors.initials: E
authors.lastname: Wanecq
authors.forename: D
authors.initials: D
authors.lastname: Prévot
authors.forename: S
authors.initials: S
authors.lastname: Grès
authors.forename: C
authors.initials: C
authors.lastname: Carpéné
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000273:Adipose Tissue / Q000201:enzymology* / Q000378:metabolism*; D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics*; D000818:Animals; D001596:Benzylamines / Q000378:metabolism / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D006632:Histamine / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008066:Lipolysis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010084:Oxidation-Reduction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012663:Semicarbazides / Q000494:pharmacology
chemical_list: D001596:Benzylamines; D015815:Cell Adhesion Molecules; D008996:Monoamine Oxidase Inhibitors; D012663:Semicarbazides; C010059:carbamylhydrazine; D006632:Histamine; C030796:benzylamine; D006861:Hydrogen Peroxide; D006631:Amine Oxidase (Copper-Containing); C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse