INSERM U858, IFR 150, I2MR, Université Toulouse III Paul-Sabatier, CHU Rangueil, Toulouse, France.
Inflamm Res. 2010 Mar;59 Suppl 2:S227-9. doi: 10.1007/s00011-009-0129-0.
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.
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.
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.
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.
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.
组胺能状态可以改变脂肪组织（AT）的发育：无组胺的小鼠表现出内脏肥胖，而 H3 拮抗剂的治疗可减少体重增加。然而，直接的组胺对 AT 的影响仍记录甚少：已经观察到，当胺氧化酶（AO）抑制剂如氨基脲阻断组胺的氧化时，组胺刺激啮齿动物脂肪细胞的脂解。
本研究的目的是研究 AOC3 基因失活（编码半卡巴嗪敏感 AO [SSAO]）对 AT 中组胺氧化和组胺脂解活性的影响。
通过实时 PCR 确定野生型（WT）和 SSAO 缺陷（AOC3-KO）小鼠中 AOC-和 MAO-编码基因的表达。通过分离的脂肪细胞中的甘油释放评估脂解作用，通过肾、回肠和 AT 中底物诱导的过氧化氢形成评估 AO 活性。
AOC3-KO 小鼠的 AT 中编码 AOC1、AOC2 或 MAOA 和 MAOB 的基因表达水平没有改变。在 WT 小鼠中，AT 中的组胺氧化低于参考 SSAO 底物苄胺，但回肠中并非如此。苄胺氧化的数量级为 AT > 回肠 > > 肾。在 AOC3-KO 小鼠中，所有组织中的苄胺氧化均被消除，而 AT 中的组胺氧化被消除，但回肠中未被消除。组胺在 WT 脂肪细胞中对脂解无作用，但刺激 AOC3-KO 脂肪细胞中的脂解，但其作用强度不及β-肾上腺素能刺激的强度。
在肠道中，组胺主要被二胺氧化酶（AOC1 产物）氧化，但在 AT 中被 SSAO（AOC3 产物）氧化。当在 AT 中免受 SSAO 氧化保护时，组胺在 AOC3-KO 小鼠的脂肪细胞中适度激活脂解。
