The circadian rhythm and lipid metabolism in organisms are tightly coupled, yet the role of lncRNAs in the integration of these two important physiological processes remains unclear. In this study, we identified a liver-specific lncRNA named HlncRNA-1, which regulates lipid metabolism while responding to circadian rhythms. Mice overexpressing HlncRNA-1 exhibited suppressed liver fat accumulation under conditions of both nutrient surplus and deficiency, along with improved insulin sensitivity. At the molecular level, ChIP assays demonstrate that Dhx9 directly occupies the HlncRNA-1 promoter, tethering circadian clock signals to this lncRNA. HlncRNA-1 subsequently recruits Hdlbp to coordinate hepatic lipid catabolism. In summary, HlncRNA-1 serves as a regulatory conduit that translates circadian clock cues into metabolic outputs, orchestrating circadian control of hepatic lipid metabolism, and activating this lncRNA represents a viable target for precisely intervening in lipid metabolic disorders induced by circadian disruption. The liver-specific lncRNA HlncRNA-1 integrates circadian and metabolic signals. Dhx9 directly binds its promoter, linking clock inputs, while HlncRNA-1 recruits Hdlbp to coordinate lipid catabolism. Overexpression suppresses hepatic steatosis and improves insulin sensitivity across nutritional states. This study identifies HlncRNA-1 as a therapeutic target for circadian disruption-induced metabolic disorders
Sun et al. (Wed,) studied this question.