Loss of Hilnc prevents diet-induced hepatic steatosis through binding of IGF2BP2
Autor: | Zhao Zhang, Man Jiang, Moubin Lin, Jiayin Peng, Hailong Wu, Yiao Jiang, Liya Ma, Dong Gao, Yun Zhao, Jiawen Song, Jia Wang, Juan He, Yuang Wang |
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Rok vydání: | 2021 |
Předmět: |
Endocrinology
Diabetes and Metabolism Gene Expression Diet High-Fat medicine.disease_cause Article Cell Line Mice Physiology (medical) Internal Medicine medicine Animals Humans Hedgehog Proteins Obesity Hedgehog Mice Knockout Messenger RNA Mutation Chemistry Gene Expression Profiling RNA-Binding Proteins RNA Lipid metabolism Cell Biology Peroxisome medicine.disease Immunohistochemistry Hedgehog signaling pathway Cell biology Fatty Liver PPAR gamma Gene Knockdown Techniques Gene Targeting Hepatocytes RNA Long Noncoding Disease Susceptibility Steatosis Biomarkers Protein Binding Signal Transduction |
Zdroj: | Nat Metab |
ISSN: | 2522-5812 |
Popis: | 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 (HilncBM/BM) decreases the expression of Hilnc in vitro and in vivo. HilncBM/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 Pparγ 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. |
Databáze: | OpenAIRE |
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