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- W3215099327 abstract "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." @default.
- W3215099327 created "2021-12-06" @default.
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- W3215099327 creator A5090587270 @default.
- W3215099327 date "2021-11-01" @default.
- W3215099327 modified "2023-10-13" @default.
- W3215099327 title "The asymmetric Pitx2 gene regulates gut muscular-lacteal development and protects against fatty liver disease" @default.
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