The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
An exercise-inducible metabolite that suppresses feeding and obesity
Open accessAbstract
Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases 1-5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear 6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A recent study revealed that lactate reduced appetite via N-lactoyl-phenylalanine (Lac-Phe) and exerted neuroplastic effects through the BDNF pathway [58].”
From High-intensity interval training or lactate administration combined with aerobic training enhances visceral fat loss while promoting VMH neuroplasticity in female rats (2024) · cites this paper as [58]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Smith, C. A., Want, E. J., O’Maille, G., Abagyan, R. A., & Siuzdak, G. E. (2006) · Analytical Chemistry · doi:10.1021/ac051437y · Cited by 5,296
Improved vectors and genome-wide libraries for CRISPR screening
Sanjana, N. E., Shalem, O., & Zhang, F. (2014) · Nature Methods · doi:10.1038/nmeth.3047 · Cited by 5,239
Genetic studies of body mass index yield new insights for obesity biology
Study, T. L. C., Locke, A. E., The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The, G. L. G. C., The, I. C. B. P., The MAGIC Investigators, The MuTHER Consortium, et al. (2015) · Nature · doi:10.1038/nature14177 · Cited by 4,534
Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris
The Tabula Muris Consortium, coordination, O., coordination, L., processing, O. C. A., sequencing, L. P. A., analysis, C. D., annotation, C. T., Writing group, Supplemental text writing group, & Principal investigators (2018) · Nature · doi:10.1038/s41586-018-0590-4 · Cited by 2,842
Primary Prevention of Coronary Heart Disease in Women through Diet and Lifestyle
Stampfer, M. J., Hu, F. B., Manson, J. E., Rimm, E. B., & Willett, W. C. (2000) · New England Journal of Medicine · doi:10.1056/nejm200007063430103 · Cited by 1,794
Physical activity and reduced occurrence of non–insulin-dependent diabetes mellitus
Helmrich, S. P., Ragland, D. R., Leung, R. W., & Paffenbarger, R. S. (1991) · New England Journal of Medicine · doi:10.1056/nejm199107183250302 · Cited by 1,634
Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes
Rawshani, A., Rawshani, A., Franzén, S., Sattar, N., Eliasson, B., Svensson, A.-M., Zethelius, B., Miftaraj, M., McGuire, D. K., Rosengren, A., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1800256 · Cited by 1,475
Eriksson, K. F., & Lindg�rde, F. (1991) · Diabetologia · doi:10.1007/bf00400196 · Cited by 1,092
Agudelo, L. Z., Femenía, T., Orhan, F., Porsmyr-Palmertz, M., Goiny, M., Martinez-Redondo, V., Correia, J. C., Izadi, M., Bhat, M., Schuppe-Koistinen, I., et al. (2014) · Cell · doi:10.1016/j.cell.2014.07.051 · Cited by 739
Roberts, L. D., Boström, P., O’Sullivan, J. F., Schinzel, R. T., Lewis, G. D., Dejam, A., Lee, Y.-K., Palma, M. J., Calhoun, S., Georgiadi, A., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.003 · Cited by 643
Cited by
Sorted by citations
Multi-Omics Profiling for Health
Babu, M., & Snyder, M. P. (2023) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2023.100561 · Cited by 434
“(121) discovered an exercise-induced metabolite, N-lactoyl-phenylalanine (LacPhe), as a suppressor of feeding and obesity in mouse,”
BackgroundSelf-citationExercise Metabolism and Adaptation in Skeletal Muscle
Smith, J. A. B., Murach, K. A., Dyar, K. A., & Zierath, J. R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00606-x · Cited by 342
Western diets and chronic diseases
Adolph, T. E., & Tilg, H. (2024) · Nature Medicine · doi:10.1038/s41591-024-03165-6 · Cited by 224
“Moreover, unequivocal experimental evidence in mice recently corroborated that perturbation of the gut microbiota by a Western diet serves as a driver of obesity and metabolic dysregulation, which provides novel druggable insights 74–79 .”
The role of efferocytosis‐fueled macrophage metabolism in the resolution of inflammation
Schilperoort, M., Ngai, D., Sukka, S. R., Avrampou, K., Shi, H., & Tabas, I. A. (2023) · Immunological Reviews · doi:10.1111/imr.13214 · Cited by 184
“169 We therefore think it would be interesting to examine whether Lac-Phe or other novel lactate-derived metabolites could also have pro-resolving and pro-efferocytosis effects in tissue repair and disease.”
BackgroundSarcopenia and Cognitive Decline in Older Adults: Targeting the Muscle–Brain Axis
Arosio, B., Calvani, R., Ferri, E., Coelho-Junior, H. J., Carandina, A., Campanelli, F., Ghiglieri, V., Marzetti, E., & Picca, A. (2023) · Nutrients · doi:10.3390/nu15081853 · Cited by 165
“An increase in the levels of N-lactoyl-phenylalanine, which reduces appetite and obesity risk, has also been reported during exercise [144].”
Background
Metadata
- Authors
- Li, V. L., He, Y., Contrepois, K., Liu, H., Kim, J. T., Wiggenhorn, A. L., Tanzo, J. T., Tung, A. S.-H., Lyu, X., Zushin, P.-J. H., Jansen, R. S., Michael, B., Loh, K. Y., Yang, A. C., Carl, C. S., Voldstedlund, C. T., Wei, W., Terrell, S. M., Moeller, B. C., Arthur, R. M., Wallis, G. A., van de Wetering, K., Stahl, A., Kiens, B., Richter, E. A., Banik, S. M., Snyder, M. P., Xu, Y., & Long, J. Z.
- Affiliations
- Stanford Medicine (US)
- Baylor College of Medicine (US)
- University of California, Berkeley (US)
- Radboud University Nijmegen (NL)
- Stanford University (US)
- University of California, San Francisco (US)
- University of Copenhagen (DK)
- University of California, Davis (US)
- University of Birmingham (GB)
- Corresponding author
- Xu, Yong
- Long, Jonathan Z.
- ORCID
- Li, Veronica L.
- He, Yang
- Contrepois, Kévin
- Liu, Hailan
- Kim, Joon T.
- Wiggenhorn, Amanda L.
- Tanzo, Julia T.
- Tung, Alan Sheng-Hwa
- Lyu, Xuchao
- Zushin, Peter-James H.
- Jansen, Robert S.
- Michael, Basil
- Loh, Kang Yong
- Yang, Andrew C.
- Carl, Christian S.
- Voldstedlund, Christian T.
- Wei, Wei
- Terrell, Stephanie M.
- Moeller, Benjamin C.
- Wallis, Gareth A.
- van de Wetering, Koen
- Stahl, Andreas
- Kiens, Bente
- Richter, Erik A.
- Banik, Steven M.
- Snyder, Michael P.
- Xu, Yong
- Long, Jonathan Z.
- Venue
- Nature
- Published
- 2022-06-15
- Volume
- 606
- Issue
- 7915
- Pages
- 785-790
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC9767481
- OpenAlex
- W4282972916
- Cited by
- 331
- References
- 31
- Citations by year
- 2026: 69 · 2025: 91 · 2024: 86 · 2023: 61 · 2022: 24
- FWCI
- 34.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (publishedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- U.S. Department of Agriculture (51000-064-01S)
- American Heart Association (20POST35120600)
- Novo Nordisk
- Novo Nordisk Fonden (NNF18OC0034072, NNF17OC0027274)
- Ono Pharma Foundation
- National Institutes of Health (DK130541, 51000-064-01S, DK113954)
- National Institute of General Medical Sciences (T32GM113854)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124265, R01DK120858, R01DK118940, P01DK113954, R01DK126830, R01DK117281, R01DK115761, DP1DK130641, R01DK109934, P30DK020579)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR072695)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- physical activity, feeding inhibition, obesity, dietary intake, energy balance, lactate, phenylalanine, CNDP2, macrophages, monocytes, glucose homeostasis, diet-induced obesity, exercise training, racehorses
- MeSH terms
- Animals, Body Weight, Diabetes Mellitus, Type 2, Disease Models, Animal, Eating, Energy Metabolism, Feeding Behavior, Glucose, Obesity, Phenylalanine, Physical Conditioning, Animal, Lactic Acid, Adiposity, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
