Open AccessLoss of Hilnc prevents diet-induced hepatic steatosis through binding of IGF2BP2
Author(s) -
Yiao Jiang,
Jiahui Peng,
Jiawen Song,
Juan He,
Man Jiang,
Jia Wang,
Lixin Ma,
Yuan Wang,
Moubin Lin,
Hailong Wu,
Zhao Zhang,
Dong Gao,
Yun Zhao
Publication year - 2021
Publication title -
nature metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.834
H-Index - 22
ISSN - 2522-5812
DOI - 10.1038/s42255-021-00488-3
Subject(s) - steatosis , lipid metabolism , hedgehog signaling pathway , hedgehog , biology , medicine , endocrinology , peroxisome proliferator activated receptor , receptor , signal transduction , metabolism , microbiology and biotechnology , biochemistry
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 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.