Revisiting PPARγ as a new friend of GPR120 in the treatment of metabolic disorders.

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.