| First Author | Hu S | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 8 | Pages | 110030 |
| PubMed ID | 34818545 | Mgi Jnum | J:321245 |
| Mgi Id | MGI:6883751 | Doi | 10.1016/j.celrep.2021.110030 |
| Citation | Hu S, et al. (2021) The asymmetric Pitx2 gene regulates gut muscular-lacteal development and protects against fatty liver disease. Cell Rep 37(8):110030 |
| abstractText | Intestinal lacteals are essential lymphatic channels for absorption and transport of dietary lipids and drive the pathogenesis of debilitating metabolic diseases. However, organ-specific mechanisms linking lymphatic dysfunction to disease etiology remain largely unknown. In this study, we uncover an intestinal lymphatic program that is linked to the left-right (LR) asymmetric transcription factor Pitx2. We show that deletion of the asymmetric Pitx2 enhancer ASE alters normal lacteal development through the lacteal-associated contractile smooth muscle lineage. ASE deletion leads to abnormal muscle morphogenesis induced by oxidative stress, resulting in impaired lacteal extension and defective lymphatic system-dependent lipid transport. Surprisingly, activation of lymphatic system-independent trafficking directs dietary lipids from the gut directly to the liver, causing diet-induced fatty liver disease. Our study reveals the molecular mechanism linking gut lymphatic function to the earliest symmetry-breaking Pitx2 and highlights the important relationship between intestinal lymphangiogenesis and the gut-liver axis. |
