| First Author | Jiang Y | Year | 2021 |
| Journal | Nat Metab | Volume | 3 |
| Issue | 11 | Pages | 1569-1584 |
| PubMed ID | 34750570 | Mgi Jnum | J:322340 |
| Mgi Id | MGI:7258186 | Doi | 10.1038/s42255-021-00488-3 |
| Citation | Jiang Y, et al. (2021) Loss of Hilnc prevents diet-induced hepatic steatosis through binding of IGF2BP2. Nat Metab 3(11):1569-1584 |
| abstractText | The Hedgehog (Hh) signalling pathway plays a critical role in regulating liver lipid metabolism and related diseases. However, the underlying mechanisms are poorly understood. Here, we show that the Hh signalling pathway induces a previously undefined long non-coding RNA (Hilnc, Hedgehog signalling-induced long non-coding RNA), which controls hepatic lipid metabolism. Mutation of the Gli-binding sites in the Hilnc promoter region (Hilnc(BM/BM)) decreases the expression of Hilnc in vitro and in vivo. Hilnc(BM/BM) and Hilnc-knockout mice are resistant to diet-induced obesity and hepatic steatosis through attenuation of the peroxisome proliferator-activated receptor signalling pathway, as Hilnc directly interacts with IGF2BP2 to enhance Ppargamma mRNA stability. Furthermore, we identify a potential functional human homologue of Hilnc, h-Hilnc, which has a similar function in regulating cellular lipid metabolism. These findings uncover a critical role of the Hh-Hilnc-IGF2BP2 signalling axis in lipid metabolism and suggest a potential therapeutic target for the treatment of diet-induced hepatic steatosis. |
