| First Author | Nelson VL | Year | 2018 |
| Journal | Genes Dev | Volume | 32 |
| Issue | 15-16 | Pages | 1035-1044 |
| PubMed ID | 30006480 | Mgi Jnum | J:276103 |
| Mgi Id | MGI:6284246 | Doi | 10.1101/gad.312355.118 |
| Citation | Nelson VL, et al. (2018) PPARgamma is a nexus controlling alternative activation of macrophages via glutamine metabolism. Genes Dev 32(15-16):1035-1044 |
| abstractText | The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that peritoneal macrophage respiration is enhanced by rosiglitazone, an activating PPARgamma ligand, in a PPARgamma-dependent manner. Moreover, PPARgamma is required for macrophage respiration even in the absence of exogenous ligand. Unexpectedly, the absence of PPARgamma dramatically affects the oxidation of glutamine. Both glutamine and PPARgamma have been implicated in alternative activation (AA) of macrophages, and PPARgamma was required for interleukin 4 (IL4)-dependent gene expression and stimulation of macrophage respiration. Indeed, unstimulated macrophages lacking PPARgamma contained elevated levels of the inflammation-associated metabolite itaconate and express a proinflammatory transcriptome that, remarkably, phenocopied that of macrophages depleted of glutamine. Thus, PPARgamma functions as a checkpoint, guarding against inflammation, and is permissive for AA by facilitating glutamine metabolism. However, PPARgamma expression is itself markedly increased by IL4. This suggests that PPARgamma functions at the center of a feed-forward loop that is central to AA of macrophages. |
