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.
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。