Evidence map›Paper›PMID 32681035›Full record

ArticleNature communications2020

An FGF15/19-TFEB regulatory loop controls hepatic cholesterol and bile acid homeostasis.

Yifeng Wang, Sumedha Gunewardena, Feng Li, David J Matye, Cheng Chen, Xiaojuan Chao, Taeyoon Jung, Yuxia Zhang, Maciej Czerwiński, Hong-Min Ni and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
4.3field-weighted citation impact, top 4% 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

58 citing papers in PubMed, 92 citations in OpenAlex.

  1. Bile acid signaling in health and disease.Molecular biomedicine · 2026
    Review
  2. The Role of Gut Microbiota in Liver Regeneration After Partial Hepatectomy: New Evidence From Animal and Human Studies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  3. Article
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  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025
    Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. MondoA and AKI and AKI-to-CKD Transition.Journal of the American Society of Nephrology : JASN · 2024
    Article
  18. Review
  19. Animals : an open access journal from MDPI · 2024
    Article
  20. Osteocytes/Osteoblasts Produce SAA3 to Regulate Hepatic Metabolism of Cholesterol.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    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 4 institutions in 1 country.

Yifeng WangDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Sumedha GunewardenaDepartment of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Feng LiDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
David J MatyeDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Cheng ChenDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Xiaojuan ChaoDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Taeyoon JungDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.ORCID http://orcid.org/0000-0002-4121-4190
Yuxia ZhangDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Maciej CzerwińskiSekisui XenoTech LLC, Kansas City, KS, 66103, USA.
Hong-Min NiDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Wen-Xing DingDepartment of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.ORCID http://orcid.org/0000-0002-3167-5073
Tiangang LiHarold Hamm Diabetes Center, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. tiangang-li@ouhsc.edu.ORCID http://orcid.org/0000-0001-8568-0129
University of Kansas Medical Center · USBaylor College of Medicine · USSekisui XenoTech (United States) · USUniversity of Oklahoma Health Sciences Center · US

Funding

THE ROLE OF HUMAN PXR IN ANTI-TUBERCULOSIS DRUG-INDUCED LIVER INJURYP20RR021940 · NCRR · UNIVERSITY OF KANSAS MEDICAL CENTER · PI COPPLE, BRYAN L · 2006 to 2011
$12.1M
Nuclear Receptors in Liver Health and DiseaseP20GM103549 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI JAESCHKE, HARTMUT W. · 2012 to 2015
$8.1M
Pilot Grants ProgramP30GM118247 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI JAESCHKE, HARTMUT W. · 2016 to 2020
$5.5M
Mechanisms regulating autophagy in alcohol-induced liver injuryR37AA020518 · NIAAA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Wen-Xing Ding · 2019 to 2026
$3.2M
Regulation of Bile Acid Metabolism and Signaling in Metabolic DiseasesR01DK117965 · NIDDK · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Tiangang Li · 2019 to 2026
$2.7M
Mechanisms regulating autophagy in alcohol-induced liver injuryR01AA020518 · NIAAA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI DING, WEN-XING · 2011 to 2018
$2.3M
NCRR NIH HHS P20 RR021940NIAAA NIH HHS R01 AA020518NIAAA NIH HHS R37 AA020518NIDDK NIH HHS R01 DK117965NIGMS NIH HHS P20 GM103549NIGMS NIH HHS P30 GM118247
6 · The paper itself

Abstract

Bile acid synthesis plays a key role in regulating whole body cholesterol homeostasis. Transcriptional factor EB (TFEB) is a nutrient and stress-sensing transcriptional factor that promotes lysosomal biogenesis. Here we report a role of TFEB in regulating hepatic bile acid synthesis. We show that TFEB induces cholesterol 7α-hydroxylase (CYP7A1) in human hepatocytes and mouse livers and prevents hepatic cholesterol accumulation and hypercholesterolemia in Western diet-fed mice. Furthermore, we find that cholesterol-induced lysosomal stress feed-forward activates TFEB via promoting TFEB nuclear translocation, while bile acid-induced fibroblast growth factor 19 (FGF19), acting via mTOR/ERK signaling and TFEB phosphorylation, feedback inhibits TFEB nuclear translocation in hepatocytes. Consistently, blocking intestinal bile acid uptake by an apical sodium-bile acid transporter (ASBT) inhibitor decreases ileal FGF15, enhances hepatic TFEB nuclear localization and improves cholesterol homeostasis in Western diet-fed mice. This study has identified a TFEB-mediated gut-liver signaling axis that regulates hepatic cholesterol and bile acid homeostasis.

Indexed as

AnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBile Acids and SaltsCell LineCholesterolCholesterol 7-alpha-HydroxylaseDiet, WesternDisease Models, AnimalFibroblast Growth FactorsHep G2 CellsHumansHypercholesterolemiaIleumLiverMaleMiceBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBile Acids and SaltsCholesterolCholesterol 7-alpha-HydroxylaseCYP7A1 protein, humanCyp7a1 protein, mouseFGF19 protein, humanfibroblast growth factor 15, mouseFibroblast Growth FactorsOrganic Anion Transporters, Sodium-Dependentsodium-bile acid cotransporterSymportersTcfeb protein, mouseTFEB protein, human

Identifiers

PMID32681035
PMCPMC7368063
OpenAlexW3043573938

What Socratic holds

Textmetadata
LicenceCC BY
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.