ArticleNature metabolism2025
Lac-Phe induces hypophagia by inhibiting AgRP neurons in mice.
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Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.
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6citing papers in PubMed
–field-weighted citation impact
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Who cites it
6 citing papers in PubMed.
- Lactate Biology: Subcellular Routing and Chemical Form Define Function.Biochemistry · 2026Review
- Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure.Current obesity reports · 2026Review
- Lactate as a Chemical Modification on Proteins and Metabolites.Annual review of biochemistry · 2026Review
- 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
- Beyond exercise and appetite: The expanding biology and therapeutic potential of N-lactoyl-phenylalanine.The Journal of pharmacology and experimental therapeutics · 2026Review
- Awareness, Perceptions, Willingness, and Feasibility of mHealth Apps Among People Living With Epilepsy: Cross-Sectional Questionnaire Study.JMIR formative research · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
30 authors.
Hailan Liu *USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Veronica L Li *Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8888-3853
Qingzhuo Liu *USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0009-0003-1243-2783
Yao LiuJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0126-8055
Cunjin SuInstitute of Molecular Medicine, McGovern Medical School, University of Texas Health Center at Houston, Houston, TX, USA.
Hueyxian WongJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.ORCID http://orcid.org/0009-0006-2832-3225
Na YinUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Hesong LiuUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Xing FangUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Kristine M McDermottUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-9525-4606
Hueyzhong WongUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Meng YuUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-8007-3378
Longlong TuUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Jonathan C BeanUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-8007-2383
Yongxiang LiUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Mengjie WangUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Yue DengUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-8874-911X
Yuhan ShiUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Olivia Z GinnardUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-8175-6357
Yuxue YangUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Junying HanUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Megan E BurtUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Sanika V JossyUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Chunmei WangUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Yongjie YangUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Benjamin R ArenkielJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9047-2420
Dong KongDivision of Endocrinology, F.M. Kirby Neurobiology Center, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7676-2074
Yang HeJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA. yang.he@bcm.edu.ORCID http://orcid.org/0000-0002-7460-5649
Jonathan Z LongDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA. jzlong@stanford.edu.ORCID http://orcid.org/0000-0003-2631-7463
Yong XuUSDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. yongxu@usf.edu.ORCID http://orcid.org/0000-0002-4908-1572
Funding
Steps towards a paternal gene activation therapy for Angelman syndromeU54HD083092 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI NELSON, DAVID LOREN, NEUL, JEFFREY L · 2014 to 2019
$7.8MR01 Application:Genetically Dissecting Cholinergic Signaling in Body Weight Control.R01DK109934 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Benjamin R Arenkiel, Qingchun Tong · 2016 to 2026
$5.4MNeurobiology for Lac-Phe HypophagiaR01DK136479 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI YONG XU · 2023 to 2026
$2.5MRole of a lactate-derived signaling metabolite in tissue crosstalk and energy balanceR01DK136526 · NIDDK · STANFORD UNIVERSITY · PI Jonathan Z Long · 2023 to 2026
$2.0MA CHOLINERGIC NEUROCIRCUIT REGULATES FEEDING BEHAVIORR01DK138518 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Benjamin R Arenkiel, YONG XU · 2024 to 2026
$1.9MTargeting olfactory neural pathways to combat obesityR01DK140538 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Yang He · 2024 to 2026
$1.6M5-HT NEURONS AND MEAL REGULATIONF32DK134121 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI MCDERMOTT, KRISTINE MARIE · 2023 to 2025
$225kAmerican Heart Association (American Heart Association, Inc.) 23POST1030352NICHD NIH HHS U54 HD083092NIDDK NIH HHS F32 DK134121NIDDK NIH HHS R01 DK109934NIDDK NIH HHS R01 DK136479NIDDK NIH HHS R01 DK136526NIDDK NIH HHS R01 DK138518NIDDK NIH HHS R01 DK140538
Abstract
N-Lactoyl-phenylalanine (Lac-Phe) is a lactate-derived circulating metabolite that reduces feeding and obesity, but the molecular mechanisms that underlie the metabolic benefits of Lac-Phe remain unknown. Here we show that Lac-Phe directly inhibits hypothalamic neurons that express Agouti-related protein (AgRP), resulting in an indirect activation of anorexigenic neurons in the paraventricular nucleus of the hypothalamus (PVH). Both AgRP inhibition and PVH activation are required to mediate Lac-Phe-induced hypophagia. Lac-Phe-mediated inhibition of AgRP neurons occurs through activation of the ATP-sensitive potassium (K
Indexed as
Agouti-Related ProteinLactatesNeuronsPhenylalanineAnimalsHypothalamusKATP ChannelsMaleMiceMice, Inbred C57BLParaventricular Hypothalamic NucleusAgouti-Related ProteinAgrp protein, mouseKATP ChannelsLactatesN-lactoyl-phenylalaninePhenylalanine
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