| First Author | Zhao M | Year | 2020 |
| Journal | Cell Rep | Volume | 32 |
| Issue | 6 | Pages | 108013 |
| PubMed ID | 32783937 | Mgi Jnum | J:301789 |
| Mgi Id | MGI:6489187 | Doi | 10.1016/j.celrep.2020.108013 |
| Citation | Zhao M, et al. (2020) Protein O-GlcNAc Modification Links Dietary and Gut Microbial Cues to the Differentiation of Enteroendocrine L Cells. Cell Rep 32(6):108013 |
| abstractText | Intestinal L cells regulate a wide range of metabolic processes, and L-cell dysfunction has been implicated in the pathogenesis of obesity and diabetes. However, it is incompletely understood how luminal signals are integrated to control the development of L cells. Here we show that food availability and gut microbiota-produced short-chain fatty acids control the posttranslational modification on intracellular proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) in intestinal epithelial cells. Via FOXO1 O-GlcNAcylation, O-GlcNAc transferase (OGT) suppresses expression of the lineage-specifying transcription factor Neurogenin 3 and, thus, L cell differentiation from enteroendocrine progenitors. Intestinal epithelial ablation of OGT in mice not only causes L cell hyperplasia and increased secretion of glucagon-like peptide 1 (GLP-1) but also disrupts gut microbial compositions, which notably contributes to decreased weight gain and improved glycemic control. Our results identify intestinal epithelial O-GlcNAc signaling as a brake on L cell development and function in response to nutritional and microbial cues. |
