Evidence map›Paper›PMID 40638391›Full record

ArticleCell reports2025

ANGPTL3 orchestrates hepatic fructose sensing and metabolism.

Meng Zhao, Karen Y Linde-Garelli, Zeyuan Zhang, David Toomer, Saranya C Reghupaty, John Isaiah Jimenez, Laetitia Coassolo, Lianna W Wat, Daniel Fernandez, Katrin J Svensson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
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

10 authors.

Meng ZhaoDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, Stanford, USA; Department of Animal Science, University of California Davis, CA, Davis, USA.
Karen Y Linde-GarelliDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Zeyuan ZhangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, Stanford, USA.
David ToomerDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Saranya C ReghupatyDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, Stanford, USA.
John Isaiah JimenezDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, Stanford, USA.
Laetitia CoassoloDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, Stanford, USA.
Lianna W WatDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, Stanford, USA.
Daniel FernandezMacromolecular Structure Knowledge Center (MSKC), Stanford University, Stanford, CA 94305, USA; Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA.
Katrin J SvenssonDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, Stanford, USA. Electronic address: katrinjs@stanford.edu.

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI MICHAEL KENNEY · 2007 to 2026
$71.4M
Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
Mechanisms controlling fructose uptake and utilizationR01DK125260 · NIDDK · STANFORD UNIVERSITY · PI Katrin Jennifer Svensson · 2020 to 2026
$3.5M
The role of circulating Slit2 in adipose thermogenesis and diabetesR00DK111916 · NIDDK · STANFORD UNIVERSITY · PI SVENSSON, KATRIN JENNIFER · 2018 to 2020
$731k
Investigating Isthmin as an adipose-to-muscle messenger that promotes muscle protein synthesisR00AR081618 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Meng Zhao · 2025 to 2026
$436k
Investigating Isthmin as an adipose-to-muscle messenger that promotes muscle protein synthesisK99AR081618 · NIAMS · STANFORD UNIVERSITY · PI ZHAO, MENG · 2023 to 2024
$182k
The role of circulating Slit2 in adipose thermogenesis and diabetesK99DK111916 · NIDDK · DANA-FARBER CANCER INST · PI SVENSSON, KATRIN JENNIFER · 2016 to 2017
$180k
American Heart Association-American Stroke Association 23IPA1042031NCI NIH HHS P30 CA124435NIAMS NIH HHS K99 AR081618NIAMS NIH HHS R00 AR081618NIDDK NIH HHS K99 DK111916NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R00 DK111916NIDDK NIH HHS R01 DK125260
6 · The paper itself

Abstract

Fructose metabolism is linked to metabolic dysfunction-associated steatotic liver disease (MASLD), but the regulatory mechanisms governing fructose uptake remain poorly understood. Here, we demonstrate that MASLD livers exhibit increased uptake of fructose-derived carbons compared to healthy livers and identify that the MASLD hepatocyte secretome can increase fructose metabolism. By performing fractionation and untargeted proteomics, we uncover a role for Angiopoietin-like 3 (ANGPTL3) as a regulator of hepatic fructose metabolism, independent of its role as a lipoprotein lipase (LPL) inhibitor. Circulating ANGPTL3 levels increase in response to fructose exposure, consistent with an action as a fructose sensor. Angptl3 knockdown in the liver resulted in a significant reduction in the uptake of hepatic fructose metabolites in vivo and downregulation of the facilitative hepatic fructose transporter slc2a8 (GLUT8) and fructolysis enzymes. This work demonstrates the existence of extracellular control of hepatic fructose metabolism through ANGPTL3.

Indexed as

Angiopoietin-like ProteinsFructoseLiverAngiopoietin-Like Protein 3AnimalsFatty LiverHepatocytesHumansMaleMiceMice, Inbred C57BLAngiopoietin-Like Protein 3Angiopoietin-like ProteinsANGPTL3 protein, humanAngptl3 protein, mouseFructoseANGPTL3CP: MetabolismfructolysisfructoseMASLD

Identifiers

PMID40638391
PMCPMC12324827

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Registered trials

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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 OpenQuestion graph.