Evidence mapPaperPMID 41238906Full record

ArticleNature metabolism2025

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency.

Vinod Tiwari, Byungchang Jin, Olivia Sun, Edwin D J Lopez Gonzalez, Min-Hsuan Chen, Xiwei Wu, Hardik Shah, Andrew Zhang, Mark A Herman, Cassandra N Spracklen and 2 more

Abstract read
In one paragraph

Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
field-weighted citation impact
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

9 citing papers in PubMed.

  1. Review
  2. Article
  3. ChREBP-β Exacerbates Renal Tubular Disorders Caused by Fructose via ATF4.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  4. Article
  5. Influence of poly(A) sequences and genetic elements on iCre expression and induction of a hibernation-like state in mice.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026
    Article
  6. Changes in the brain [NADFrontiers in aging neuroscience · 2026
    Review
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Vinod TiwariBeckman Research Institute of City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0000-0003-2341-0953
Byungchang JinLiver Center and Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
Olivia SunBeckman Research Institute of City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0009-0009-4011-0750
Edwin D J Lopez GonzalezBeckman Research Institute of City of Hope, Duarte, CA, USA.
Min-Hsuan ChenBeckman Research Institute of City of Hope, Duarte, CA, USA.
Xiwei WuBeckman Research Institute of City of Hope, Duarte, CA, USA.
Hardik ShahComprehensive Cancer Center, University of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-8408-5686
Andrew ZhangLiver Center and Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
Mark A HermanBaylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6979-103X
Cassandra N SpracklenDepartment of Biostatistics and Epidemiology, University of Massachusetts, Amherst, MA, USA.ORCID http://orcid.org/0000-0003-3590-7182
Russell P GoodmanLiver Center and Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3881-7895
Charles BrennerBeckman Research Institute of City of Hope, Duarte, CA, USA. cbrenner@coh.org.ORCID http://orcid.org/0000-0002-4955-3226

Funding

Small Animal Studies CoreP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · 1985 to 2025
$31.1M
Genetic programming of human islet metabolic and endoplasmic reticulum (ER) stress responses in diabetesR01DK118011 · NIDDK · JACKSON LABORATORY · 2022 to 2025
$3.2M
Type 2 diabetes risk variant effects on mitochondrial (patho)physiologyR01DK136671 · JACKSON LABORATORY · 2025 to 2025
$740k
An NADH-ChREBP axis in fatty liver disease and dyslipidemiaR01DK134675 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$472k
American Diabetes Association (ADA) 11-22-JDFPM-06NCI NIH HHS P30 CA033572NHLBI NIH HHS R01 HL147545NIDDK NIH HHS R01 DK100425NIDDK NIH HHS R01 DK118011NIDDK NIH HHS R01 DK134675NIDDK NIH HHS R01 DK136671U.S. Department of Health & Human Services | National Institutes of Health (NIH) P30CA33572U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK012170U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK100425U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK118011U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK134675U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK136671U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HL147545
6 · The paper itself

Abstract

Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms part of a system that communicates metabolic states from the liver to the brain in a manner that alters food and alcohol choices. The data provide a framework for understanding FGF21 induction in varied conditions, suggest ways to develop FGF21-inducing drugs and suggest potential drug candidates for lean metabolic-dysfunction-associated steatotic liver disease and support of urea cycle function in CD.

Indexed as

Basic Helix-Loop-Helix Leucine Zipper Transcription FactorsCalcium-Binding ProteinsFibroblast Growth FactorsGlycerophosphatesLipogenesisOrganic Anion TransportersAnimalsFatty LiverHumansMiceMice, Inbred C57BLMice, KnockoutMitochondrial Membrane Transport ProteinsTranscription, Geneticalpha-glycerophosphoric acidBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCalcium-Binding ProteinscitrinFGF21 protein, humanfibroblast growth factor 21Fibroblast Growth FactorsGlycerophosphatesMitochondrial Membrane Transport ProteinsMLXIPL protein, humanMlxipl protein, mouseOrganic Anion Transporters

Identifiers

PMID41238906
PMCPMC12638245

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.