LncRNA Neat1通过昼夜节律调节肥胖

代谢和生物钟之间的关系对人类健康至关重要，因此研究代谢和生物钟之间的基因表达调控网络有助于我们改善健康。近年来，越来越多的证据表明长链非编码RNA（LncRNA）是基因表达网络中的重要调控因子。然而，我们对于LncRNA如何调控代谢和生物钟之间的关系还知之甚少。我们的研究通过敲除LncRNA Neat1基因揭示了其在代谢和生物钟之间的重要作用。具体而言，我们发现敲除Neat1可以抑制高脂肪饮食引起的肥胖，而对正常饮食没有影响。这种调节机制是由于高脂饮食通过激活NF-κB通路上调了Neat1的表达，从而使得Neat1对NONO蛋白的隔离效果加强，抑制了NONO参与的节律相关基因的转录激活，导致了节律紊乱，从而促进了肥胖。这项研究为代谢、炎症和昼夜节律之间的相互作用机制提供了新的见解。我们的研究结果突出了Neat1作为肥胖和相关疾病潜在治疗靶点的重要性。

The interplay between metabolism and the body clock is critical for maintaining human health. Investigating the gene expression regulatory network that governs this relationship can lead to improved health outcomes. Recently, mounting evidence has identified long non-coding RNAs (lncRNAs) as crucial regulators in gene expression networks. However, the mechanisms by which lncRNAs regulate metabolism and the body clock remain poorly understood. In this study, we characterized the function of the lncRNA Neat1 in the regulation of metabolism and the biological clock using a knockout model. Our results demonstrated that knockout of the Neat1 gene effectively suppresses obesity induced by a high-fat diet, with no impact on normal diet. The underlying regulatory mechanism involves the upregulation of Neat1 expression through the activation of the NF-κB pathway, which enhances the isolation of the NONO protein by Neat1, leading to the inhibition of transcriptional activation of rhythm-related genes involving NONO and ultimately causing rhythm disturbance and obesity. These findings provide novel insights into the mechanisms underlying the interplay between metabolism, inflammation, and circadian rhythms. Furthermore, our results highlight the potential of Neat1 as a therapeutic target for obesity and related disorders.