| First Author | Brocker CN | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 5847 |
| PubMed ID | 33203882 | Mgi Jnum | J:299830 |
| Mgi Id | MGI:6490716 | Doi | 10.1038/s41467-020-19554-7 |
| Citation | Brocker CN, et al. (2020) Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting. Nat Commun 11(1):5847 |
| abstractText | Exploring the molecular mechanisms that prevent inflammation during caloric restriction may yield promising therapeutic targets. During fasting, activation of the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) promotes the utilization of lipids as an energy source. Herein, we show that ligand activation of PPARalpha directly upregulates the long non-coding RNA gene Gm15441 through PPARalpha binding sites within its promoter. Gm15441 expression suppresses its antisense transcript, encoding thioredoxin interacting protein (TXNIP). This, in turn, decreases TXNIP-stimulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, caspase-1 (CASP1) cleavage, and proinflammatory interleukin 1beta (IL1B) maturation. Gm15441-null mice were developed and shown to be more susceptible to NLRP3 inflammasome activation and to exhibit elevated CASP1 and IL1B cleavage in response to PPARalpha agonism and fasting. These findings provide evidence for a mechanism by which PPARalpha attenuates hepatic inflammasome activation in response to metabolic stress through induction of lncRNA Gm15441. |
