Activated transcription factor (TF) farnesoid X receptor (FXR) represses glucagon-like peptide-1 (GLP-1) secretion in enteroendocrine L cells. This, in turn, reduces insulin secretion, which is triggered when β cells bind GLP-1. Preventing FXR activation could boost GLP-1 production and insulin secretion. Yet, FXR's broader role in L cell biology still lacks understanding. Here, we show that FXR is a multifaceted TF in L cells using proteomics and gene expression data generated on GLUTag L cells. Most striking, 252 proteins regulated upon glucose stimulation have their abundances neutralized upon FXR activation. Mitochondrial repression or glucose import block are likely mechanisms of this. Further, FXR physically targets bile acid metabolism proteins, growth factors and other TFs, regulates ChREBP, while extensive text-mining found 30 FXR-regulated proteins to be well-known in L cell biology. Taken together, this outlines FXR as a powerful TF, where GLP-1 secretion block is just one of many downstream effects.

活化的转录因子（TF）法呢类X受体（FXR）抑制肠内分泌L细胞中胰高血糖素样肽1（GLP-1）的分泌。反过来，这会减少胰岛素分泌，这是当β细胞结合GLP-1时触发的。阻止FXR激活可以提高GLP-1的产生和胰岛素的分泌。然而，FXR在L细胞生物学中的广泛作用仍然缺乏了解。在这里，我们使用蛋白质组学和在GLUTag L细胞上产生的基因表达数据，表明FXR是L细胞中的多面TF。最引人注目的是，在葡萄糖刺激下调节的252种蛋白质在FXR激活后就被中和了。线粒体抑制或葡萄糖输入阻滞可能是其机制。此外，FXR在物理上靶向胆汁酸代谢蛋白，生长因子和其他TF，调节ChREBP，同时大量的文本挖掘发现30种FXR调节的蛋白在L细胞生物学中是众所周知的。两者合计，这将FXR概述为功能强大的TF，其中GLP-1分泌阻滞只是许多下游效应之一。