ArticleNature metabolism2024
Lac-Phe mediates the effects of metformin on food intake and body weight.
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Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52citing papers in PubMed
15.7field-weighted citation impact, top 1% of its field
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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.
Who cites it
52 citing papers in PubMed, 67 citations in OpenAlex.
- The anti-obesogenic metabolite, Lac-Phe, is elevated by metformin treatment in prostate cancer patients.EMBO molecular medicine · 2026Trial
- Exercise intensity determines circulating levels of Lac-Phe and other exerkines: a randomized crossover trial.Metabolomics : Official journal of the Metabolomic Society · 2025Trial
- Metformin Treatment With or Without Mediterranean Diet for the Prevention of Age-Related Diseases in People With Metabolic Syndrome: The MeMeMe Randomized Trial.Diabetes care · 2025Trial
- LC-MS/MS quantification of N-lactoyl-phenylalanine and N-lactoyl-tyrosine in human plasma: method validation and clinical application to metformin administration.Translational and clinical pharmacology · 2026Article
- Metabolite and nutrient regulation of macrophages in obesity and metabolic disease.Nature reviews. Immunology · 2026Review
- Lactate Biology: Subcellular Routing and Chemical Form Define Function.Biochemistry · 2026Review
- The blood metabolome of brain health in midlife and influences of genes, microbiome and exposome.Nature aging · 2026Article
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure.Current obesity reports · 2026Review
- Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control.Nature metabolism · 2026Article
- The hypothalamus as a therapeutic target: Towards novel approaches for managing antipsychotic-induced weight gain.Reviews in endocrine & metabolic disorders · 2026Review
- Metabotherapy for intestinal disease: using metabolites to prevent and treat disorders of the gut.Nature reviews. Gastroenterology & hepatology · 2026Review
- Lactate as a Chemical Modification on Proteins and Metabolites.Annual review of biochemistry · 2026Review
- Lac-Phe elicits anxiolytic-like effects associated with monoaminergic signaling in mice.Translational psychiatry · 2026Article
- Muscle movement and metabolism: exercise and skeletal muscle as mediators of health-a report from the 26th Annual Harvard Nutrition Obesity Symposium, 2025.The American journal of clinical nutrition · 2026Article
- The Emerging Role of N-Lactoyl-Phenylalanine (Lac-Phe) in Metabolic Regulation and Disease: From Exercise-Induced Metabolite to Therapeutic Candidate.Antioxidants (Basel, Switzerland) · 2026Article
- Untargeted Metabolomics Identifies N-Lactoyl-Amino Acids as Dose-Responsive Plasma Biomarkers of Metformin Adherence in Type 2 Diabetes.Clinical pharmacology and therapeutics · 2026Article
- Beyond exercise and appetite: The expanding biology and therapeutic potential of N-lactoyl-phenylalanine.The Journal of pharmacology and experimental therapeutics · 2026Review
- Lac-Phe: An Emerging Appetite-Regulating Exerkine with Health and Therapeutic Benefits.Current obesity reports · 2026Review
- Exercise benefits in metabolism on cardiovascular disease.Frontiers in cardiovascular medicine · 2026Review
Corrections and comments
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Authors and funding
27 authors at 10 institutions in 1 country.
Shuke XiaoDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-2103-128X
Veronica L LiDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8888-3853
Xuchao LyuDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1967-3902
Xudong ChenDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Wei WeiDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8110-0705
Fahim AbbasiStanford Diabetes Research Center, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3932-8375
Joshua W KnowlesStanford Diabetes Research Center, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1922-7240
Alan Sheng-Hwa TungDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-0669-1928
Shuliang DengDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Gaurav TiwariDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0009-0000-2540-6005
Xu ShiDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Shuning ZhengDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Laurie FarrellDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Zsu-Zsu ChenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9441-675X
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0002-5264-5068
Mark O GoodarziDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-6364-5103
Alexis C WoodUSDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.
Yii-Der Ida ChenThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Leslie A LangeDivision of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0001-7191-1723
Clary B ClishBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8259-9245
Usman A TahirDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3657-6082
Robert E GersztenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6767-7687
Mark D Benson *Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8977-2389
Jonathan Z Long *Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. jzlong@stanford.edu.ORCID http://orcid.org/0000-0003-2631-7463
Beth Israel Deaconess Medical Center · USStanford University · USUCLA Medical Center · USBroad Institute · USCardiovascular Institute of the South · USCedars-Sinai Medical Center · USChildren's Nutrition Research Center at Baylor College of Medicine · USHoward Hughes Medical Institute · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Virginia · US
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MARTIN TORRIANI · 1994 to 2026
$31.6MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MStanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5MTask Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MTask Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1MTO EXERCISE OPTION PERIOD ONE (1) FOR TASK AREA A - MESA CORE OPERATIONS, FIELD CENTER.75N92020D00004 · NHLBI · NORTHWESTERN UNIVERSITY · PI SIEGEL, JONATHAN H · 2020 to 2025
$4.5MTask Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00006 · NHLBI · UNIVERSITY OF MINNESOTA · PI PANKOW, JAMES S · 2020 to 2025
$4.4MAmerican Heart Association-American Stroke Association 24POST1196199NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS K08 HL145095NHLBI NIH HHS K08 HL161445NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL151855NIDDK NIH HHS K23 DK127073NIDDK NIH HHS P30 DK040561NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK106236NIDDK NIH HHS R01 DK116750NIDDK NIH HHS R01 DK120565NIDDK NIH HHS R01 DK124265NIDDK NIH HHS R01 DK136526NIDDK NIH HHS R01 DK137889NIDDK NIH HHS UM1 DK078616NIGMS NIH HHS T32 GM113854
Abstract
Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin's effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2
Indexed as
Body WeightEatingMetforminAnimalsDipeptidesHumansHypoglycemic AgentsMaleMicePhenylalanineDipeptidesHypoglycemic AgentsMetforminN-lactoyl-phenylalaninePhenylalanine
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