ABSTRACT

G Protein-coupled receptor 120 (GPR120; fatty acid receptor 4, FFAR4) and PPARγ agonists both lead to anti-inflammatory and insulin sensitizing effects despite signalling through distinct pathways. We recently reported the overarching idea that these two pathways are interactive. Specifically, treatment of obese mice with the PPARγ agonist rosiglitazone (a thiazolidinedione, TZD) in combination with the GPR120 agonist compound A synergistically improves glucose tolerance and insulin sensitivity. We have deconvoluted the mechanisms underlying this feed-forward effect in the study. Taken together, our study shows that low dose TZD administration, in combination with GPR120 agonists, produces additive beneficial effects on glucose tolerance and insulin sensitivity without the undesirable adverse effects of TZD. Our study suggests potential value of combination PPARγ and GPR120 agonists to treat metabolic disease.

摘要

G蛋白偶联受体120（GPR120；脂肪酸受体4，FFAR4）和PPARγ激动剂尽管通过不同途径发出信号，但均会导致抗炎和胰岛素增敏作用。我们最近报告了这两个途径是相互作用的总体思想。具体地，用PPARγ激动剂罗格列酮（噻唑烷二酮，TZD）与GPR120激动剂化合物A组合治疗肥胖小鼠可协同改善葡萄糖耐量和胰岛素敏感性。我们在研究中反卷积了这种前馈效应的潜在机制。两者合计，我们的研究表明，低剂量的TZD给药与GPR120激动剂结合使用，对葡萄糖耐量和胰岛素敏感性产生附加的有益作用，而没有TZD的不良影响。