PDF(Pubmed)
Abstract：
GPR55 is a receptor for lysophosphatidylinositols (LPIs) in digestive metabolites. Overnutrition leads to obesity, insulin resistance, and increased LPI levels in the plasma. The involvement of LPIs and GPR55 in adiposity, hepatic steatosis, and atherosclerosis has been previously elucidated. However, the therapeutic efficacy of GPR55 antagonists against obesity-induced airway inflammation has not been studied. The present study investigated whether CID16020046, a selective antagonist of GPR55, could modulate obesity-induced airway inflammation caused by a high-fat diet (HFD) in C57BL/6 mice. Administration of CID16020046 (1 mg/kg) inhibits HFD-induced adiposity and glucose intolerance. Analysis of immune cells in BALF showed that CID16020046 inhibited HFD-induced increase in immune cell infiltration. Histological analysis revealed the HFD induced hypersecretion of mucus and extensive fibrosis in the lungs. CID16020046 inhibited these HFD-induced pathological features. qRT-PCR revealed the HFD-induced increase in the expression of Ifn-γ, Tnf-α, Il-6, Il-13, Il-17A, Il-1β, Nlrp3, and Mpo mRNAs in the lungs. CID16020046 inhibited the HFD-induced increases in these genes. The expression levels of adipokines were regulated by the HFD and CID16020046. AdipoQ in the lungs and gonadal white adipose tissue was decreased by the HFD and reversed by CID16020046. In contrast, Lep was increased by the HFD and suppressed by CID16020046. The findings suggest the potential application of the GPR55 antagonist CID16020046 in obesity-induced airway inflammation.
摘要：
GPR55是消化代谢物中溶血磷脂酰肌醇(LPI)的受体。营养过剩导致肥胖,胰岛素抵抗，血浆中LPI水平升高。LPI和GPR55参与肥胖，肝脂肪变性,动脉粥样硬化以前已经被阐明。然而,尚未研究GPR55拮抗剂对肥胖诱导的气道炎症的治疗效果.本研究调查了GPR55的选择性拮抗剂CID16020046是否可以调节由高脂饮食（HFD）引起的C57BL/6小鼠肥胖诱导的气道炎症。施用CID16020046(1mg/kg)抑制HFD诱导的肥胖和葡萄糖耐受不良。对BALF中免疫细胞的分析表明，CID16020046抑制了HFD诱导的免疫细胞浸润增加。组织学分析显示HFD诱导的粘液分泌过多和肺部广泛的纤维化。CID16020046抑制这些HFD诱导的病理特征。qRT-PCR显示HFD诱导的Ifn-γ表达增加，Tnf-α,Il-6,Il-13,Il-17A,IL-1β,肺中的Nlrp3和MpomRNA。CID16020046抑制这些基因中HFD诱导的增加。脂肪因子的表达水平受HFD和CID16020046的调控。HFD降低了肺和性腺白色脂肪组织中的AdipoQ，并通过CID16020046逆转。相比之下,Lep被HFD增加，被CID16020046抑制。研究结果表明GPR55拮抗剂CID16020046在肥胖诱导的气道炎症中的潜在应用。
