Evidence mapPaperPMID 34818545Full record

ArticleCell reports2021

The asymmetric Pitx2 gene regulates gut muscular-lacteal development and protects against fatty liver disease.

Shing Hu, Aparna Mahadevan, Isaac F Elysee, Joseph Choi, Nathan R Souchet, Gloria H Bae, Alessandra K Taboada, Bhargav Sanketi, Gerald E Duhamel, Carolyn S Sevier and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Transport functions of intestinal lymphatic vessels.Nature reviews. Gastroenterology & hepatology · 2025
    Review
  4. TRIB3 Is a Hub Gene in Steatohepatitis and Aggravates Lipid Deposition and Inflammation in Hepatocytes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025
    Article
  5. Article
  6. Article
  7. Mechanisms and functions of intestinal vascular specialization.The Journal of experimental medicine · 2024
    Review
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Shing HuDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Aparna MahadevanDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Isaac F ElyseeDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Joseph ChoiDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Nathan R SouchetDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Gloria H BaeDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Alessandra K TaboadaDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Bhargav SanketiDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Gerald E DuhamelDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Carolyn S SevierDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA.
Ge TaoDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Natasza A KurpiosDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell, Ithaca, NY 14853, USA. Electronic address: nk378@cornell.edu.
Cornell University · USMedical University of South Carolina · US

Funding

Graduate Training Program in Comparative MedicineT32OD011000 · CORNELL UNIVERSITY · 2025 to 2025
$0k
American Heart Association-American Stroke Association 17SDG33400141NIDDK NIH HHS R01 DK092776NIDDK NIH HHS R01 DK107634NIDDK NIH HHS R56 DK092776NIH HHS S10 OD018516NIH HHS S10 OD025049NIH HHS T32 OD011000
6 · The paper itself

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.

Indexed as

AnimalsBiological TransportDietary FatsDuodenumFemaleHomeobox Protein PITX2Homeodomain ProteinsIntestinal MucosaIntestinesLipid MetabolismLipidsLymphangiogenesisLymphatic VesselsMaleMiceSignal TransductionDietary FatsHomeobox Protein PITX2Homeodomain ProteinsLipidsTranscription FactorsASE enhancerdietary lipid transportfatty liver diseasegut lymphatic developmentlactealleft-right asymmetryoxidative stressPitx2portal lipid transportvillus-axial smooth muscle

Identifiers

PMID34818545
PMCPMC8650168
OpenAlexW3215099327

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.