Abstract：
BACKGROUND: Previous work suggests the existence of a paracrine signaling mechanism in which histamine released from visceral mast cells into the portal circulation contributes to fasting-induced ketogenesis by stimulating biosynthesis of the endogenous high-affinity PPAR-α agonist oleoylethanolamide (OEA).
METHODS: Male C57Bl/6J mice were rendered obese by exposure to a high-fat diet (HFD; 60% fat). We measured histamine, OEA, and other fatty-acid ethanolamides by liquid-chromatography/mass spectrometry, gene transcription by RT-PCR, protein expression by ELISA, neutral lipid accumulation in the liver using Red Oil O and BODIPY staining, and collagen levels using picrosirius red staining.
RESULTS: Long-term exposure to HFD suppressed both fasting-induced histamine release into portal blood and histamine-dependent OEA production in the liver. Additionally, subchronic OEA administration reduced lipid accumulation, inflammatory responses, and fibrosis in the liver of HFD-exposed mice.
CONCLUSIONS: The results suggest that disruption of histamine-dependent OEA signaling in the liver might contribute to pathology in obesity-associated liver steatosis.
METHODS: Male C57Bl/6J mice were rendered obese by exposure to a high-fat diet (HFD; 60% fat). We measured histamine, OEA, and other fatty-acid ethanolamides by liquid-chromatography/mass spectrometry, gene transcription by RT-PCR, protein expression by ELISA, neutral lipid accumulation in the liver using Red Oil O and BODIPY staining, and collagen levels using picrosirius red staining.
RESULTS: Long-term exposure to HFD suppressed both fasting-induced histamine release into portal blood and histamine-dependent OEA production in the liver. Additionally, subchronic OEA administration reduced lipid accumulation, inflammatory responses, and fibrosis in the liver of HFD-exposed mice.
CONCLUSIONS: The results suggest that disruption of histamine-dependent OEA signaling in the liver might contribute to pathology in obesity-associated liver steatosis.
摘要：
背景：先前的工作表明存在一种旁分泌信号机制，其中从内脏肥大细胞释放到门静脉循环中的组胺通过刺激内源性高亲和力PPAR-α激动剂油酰乙醇胺（OEA）的生物合成来促进禁食诱导的酮生成。
方法:雄性C57Bl/6J小鼠通过暴露于高脂肪饮食(HFD;60%脂肪)而变得肥胖。我们测量了组胺，OEA,和其他脂肪酸乙醇酰胺通过液相色谱/质谱，通过RT-PCR进行基因转录，通过ELISA表达蛋白，使用红油O和BODIPY染色在肝脏中的中性脂质积累，和胶原蛋白水平使用picrosirius红染色。
结果：长期暴露于HFD抑制了空腹诱导的组胺释放进入门脉血液和肝脏中组胺依赖性OEA的产生。此外,亚慢性OEA给药减少脂质积累，炎症反应，和HFD暴露小鼠肝脏中的纤维化。
结论：结果表明，肝脏中组胺依赖性OEA信号的破坏可能导致肥胖相关肝脏脂肪变性的病理。
方法:雄性C57Bl/6J小鼠通过暴露于高脂肪饮食(HFD;60%脂肪)而变得肥胖。我们测量了组胺，OEA,和其他脂肪酸乙醇酰胺通过液相色谱/质谱，通过RT-PCR进行基因转录，通过ELISA表达蛋白，使用红油O和BODIPY染色在肝脏中的中性脂质积累，和胶原蛋白水平使用picrosirius红染色。
结果：长期暴露于HFD抑制了空腹诱导的组胺释放进入门脉血液和肝脏中组胺依赖性OEA的产生。此外,亚慢性OEA给药减少脂质积累，炎症反应，和HFD暴露小鼠肝脏中的纤维化。
结论：结果表明，肝脏中组胺依赖性OEA信号的破坏可能导致肥胖相关肝脏脂肪变性的病理。
