Evidence map›Paper›PMID 39889702›Full record

ArticleCell metabolism2025

Lactate homeostasis is maintained through regulation of glycolysis and lipolysis.

Won Dong Lee, Daniel R Weilandt, Lingfan Liang, Michael R MacArthur, Natasha Jaiswal, Olivia Ong, Charlotte G Mann, Qingwei Chu, Craig J Hunter, Rolf-Peter Ryseck and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing 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

48 citing papers in PubMed.

  1. UntargetedNutrients · 2026
    Trial
  2. Article
  3. Article
  4. Review
  5. Lactate Metabolism: Separating Correlation From Causation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

19 authors.

Won Dong LeeDepartment of Chemistry, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
Daniel R WeilandtDepartment of Chemistry, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
Lingfan LiangDepartment of Chemistry, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
Michael R MacArthurDepartment of Chemistry, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
Natasha JaiswalDepartment of Health and Kinesiology, Purdue University, West Lafayette, IN, USA.
Olivia OngDepartment of Health and Kinesiology, Purdue University, West Lafayette, IN, USA.
Charlotte G MannDepartment of Health Sciences and Technology, ETH Zürich, Schwerzenbach, Switzerland.
Qingwei ChuInstitute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Craig J HunterDepartment of Chemistry, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
Rolf-Peter RyseckDepartment of Chemistry, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
Wenyun LuDepartment of Chemistry, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
Anna M OschmannDepartment of Chemistry, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
Alexis J CowanLewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA.
Tara A TeSlaaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Caroline R BartmanDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cholsoon JangDepartment of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Joseph A BaurInstitute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Paul M TitchenellInstitute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Joshua D RabinowitzDepartment of Chemistry, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ, USA; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA. Electronic address: joshr@princeton.edu.

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1986 to 2026
$48.3M
Tumor cell metabolism in actionR01CA163591 · NCI · RUTGERS, THE STATE UNIV OF N.J. · PI JOSHUA D RABINOWITZ, Eileen P. White · 2012 to 2026
$7.0M
Metabolism in Action: Quantitative Fluxes in MammalsDP1DK113643 · NIDDK · PRINCETON UNIVERSITY · PI RABINOWITZ, JOSHUA D · 2016 to 2020
$5.7M
Regulation of Skeletal Muscle Metabolism by Insulin SignalingR01DK123252 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI TITCHENELL, PAUL MICHAEL · 2020 to 2024
$2.2M
Revealing cancer metabolism via mass spectrometry and isotope tracersR50CA211437 · NCI · PRINCETON UNIVERSITY · PI Wenyun Lu · 2016 to 2026
$1.3M
Indirect calorimetry cages equipped for glucose and blood pressure telemetryS10OD025098 · OD · UNIVERSITY OF PENNSYLVANIA · PI BAUR, JOSEPH A. · 2019 to 2019
$750k
Impact of insulin on lactate metabolismF32DK127843 · NIDDK · PRINCETON UNIVERSITY · PI LEE, WON DONG · 2021 to 2023
$208k
NCI NIH HHS R01 CA163591NCI NIH HHS R50 CA211437NIDDK NIH HHS DP1 DK113643NIDDK NIH HHS F32 DK127843NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK123252NIH HHS S10 OD025098
6 · The paper itself

Abstract

Lactate is among the highest flux circulating metabolites. It is made by glycolysis and cleared by both tricarboxylic acid (TCA) cycle oxidation and gluconeogenesis. Severe lactate elevations are life-threatening, and modest elevations predict future diabetes. How lactate homeostasis is maintained, however, remains poorly understood. Here, we identify, in mice, homeostatic circuits regulating lactate production and consumption. Insulin induces lactate production by upregulating glycolysis. We find that hyperlactatemia inhibits insulin-induced glycolysis, thereby suppressing excess lactate production. Unexpectedly, insulin also promotes lactate TCA cycle oxidation. The mechanism involves lowering circulating fatty acids, which compete with lactate for mitochondrial oxidation. Similarly, lactate can promote its own consumption by lowering circulating fatty acids via the adipocyte-expressed G-protein-coupled receptor hydroxycarboxylic acid receptor 1 (HCAR1). Quantitative modeling suggests that these mechanisms suffice to produce lactate homeostasis, with robustness to noise and perturbation of individual regulatory mechanisms. Thus, through regulation of glycolysis and lipolysis, lactate homeostasis is maintained.

Indexed as

GlycolysisHomeostasisLactic AcidLipolysisAdipocytesAnimalsCitric Acid CycleFatty AcidsInsulinMaleMiceMice, Inbred C57BLOxidation-ReductionReceptors, G-Protein-CoupledFatty AcidsHcar1 protein, mouseInsulinLactic AcidReceptors, G-Protein-Coupledcompetitive catabolismdiabetes mellitusHCAR1 signalinginsulin resistanceinsulin signalinglactate metabolismmetabolic fluxmetabolic homeostasisquantitative modelingTCA cycle

Identifiers

PMID39889702
PMCPMC11926601

What Socratic holds

Textmetadata
LicenceTDM
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.