| First Author | Paschoal VA | Year | 2020 |
| Journal | Cell Metab | Volume | 31 |
| Issue | 6 | Pages | 1173-1188.e5 |
| PubMed ID | 32413335 | Mgi Jnum | J:296545 |
| Mgi Id | MGI:6469018 | Doi | 10.1016/j.cmet.2020.04.020 |
| Citation | Paschoal VA, et al. (2020) Positive Reinforcing Mechanisms between GPR120 and PPARgamma Modulate Insulin Sensitivity. Cell Metab 31(6):1173-1188.e5 |
| abstractText | G protein-coupled receptor 120 (GPR120) and PPARgamma agonists each have insulin sensitizing effects. But whether these two pathways functionally interact and can be leveraged together to markedly improve insulin resistance has not been explored. Here, we show that treatment with the PPARgamma agonist rosiglitazone (Rosi) plus the GPR120 agonist Compound A leads to additive effects to improve glucose tolerance and insulin sensitivity, but at lower doses of Rosi, thus avoiding its known side effects. Mechanistically, we show that GPR120 is a PPARgamma target gene in adipocytes, while GPR120 augments PPARgamma activity by inducing the endogenous ligand 15d-PGJ2 and by blocking ERK-mediated inhibition of PPARgamma. Further, we used macrophage- (MKO) or adipocyte-specific GPR120 KO (AKO) mice to show that GRP120 has anti-inflammatory effects via macrophages while working with PPARgamma in adipocytes to increase insulin sensitivity. These results raise the prospect of a safer way to increase insulin sensitization in the clinic. |
