Metabolism is often regulated by the transcription and translation of RNA. In turn, it is likely that some metabolites regulate enzymes controlling reversible RNA modification, such as N⁶-methyladenosine (m⁶A), to modulate RNA. This hypothesis is at least partially supported by the findings that multiple metabolic diseases are highly associated with fat mass and obesity-associated protein (FTO), an m⁶A demethylase. However, knowledge about whether and which metabolites directly regulate m⁶A remains elusive. Here, we show that NADP directly binds FTO, independently increases FTO activity, and promotes RNA m⁶A demethylation and adipogenesis. We screened a set of metabolites using a fluorescence quenching assay and NADP was identified to remarkably bind FTO. In vitro demethylation assays indicated that NADP enhances FTO activity. Furthermore, NADP regulated mRNA m⁶A via FTO in vivo, and deletion of FTO blocked NADP-enhanced adipogenesis in 3T3-L1 preadipocytes. These results build a direct link between metabolism and RNA m⁶A demethylation.

代谢通常受RNA转录和翻译的调节。反过来，一些代谢物可能调节控制可逆RNA修饰的酶，例如N ⁶ -甲基腺苷(m ⁶ A)，以调节RNA。^{这一假设至少得到了以下研究结果的部分支持：多种代谢疾病与脂肪量和肥胖相关蛋白 (FTO)（一种 m 6} A 去甲基酶）高度相关。然而，关于是否以及哪些代谢物直接调节 m ⁶ A 的知识仍然难以捉摸。在这里，我们证明 NADP 直接结合 FTO，独立增加 FTO 活性，并促进 RNA m ⁶ A 去甲基化和脂肪形成。我们使用荧光猝灭测定筛选了一组代谢物，并确定 NADP 与 FTO 显着结合。体外去甲基化测定表明 NADP 增强 FTO 活性。此外，NADP在体内通过 FTO调节 mRNA m ^{6 A，并且 FTO 的缺失阻断了 3T3-L1 前脂肪细胞中 NADP 增强的脂肪生成。这些结果在代谢和 RNA m 6} A 去甲基化之间建立了直接联系。