饮食诱导肥胖破坏了小鼠肝脏中组氨酸依赖的油酰乙醇酰胺信号传导。
Diet-Induced Obesity Disrupts Histamine-Dependent Oleoylethanolamide Signaling in the Mouse Liver.
机构信息
Department of Anatomy and Neurobiology, University of California, Irvine, California, USA.
Department of Anatomy and Neurobiology, University of California, Irvine, California, USA,
出版信息
Pharmacology. 2022;107(7-8):423-432. doi: 10.1159/000524753. Epub 2022 Jun 10.
INTRODUCTION
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.
DISCUSSION
The results suggest that disruption of histamine-dependent OEA signaling in the liver might contribute to pathology in obesity-associated liver steatosis.
简介
先前的研究表明，组胺可能通过刺激内源性高亲和力过氧化物酶体增殖物激活受体-α激动剂油酰乙醇酰胺（OEA）的生物合成，从内脏肥大细胞释放到门静脉循环中，从而形成一种旁分泌信号机制，促进禁食诱导的酮体生成。
方法
雄性 C57Bl/6J 小鼠通过高脂肪饮食（HFD；60%脂肪）暴露而肥胖。我们通过液相色谱/质谱法测量了组胺、OEA 和其他脂肪酸乙醇酰胺，通过 RT-PCR 测量了基因转录，通过 ELISA 测量了蛋白质表达，通过 Red Oil O 和 BODIPY 染色测量了肝内中性脂质积累，通过苦味酸红染色测量了胶原水平。
结果
长期暴露于 HFD 抑制了空腹诱导的组胺释放到门静脉血液中和肝脏中依赖于组胺的 OEA 产生。此外，亚慢性 OEA 给药可减少 HFD 暴露小鼠肝脏中的脂质积累、炎症反应和纤维化。
讨论
结果表明，肝内依赖于组胺的 OEA 信号的破坏可能导致肥胖相关脂肪性肝病的病理。
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