Author
Listed:
- Veronica L. Li
(Stanford University School of Medicine
Stanford University
Stanford University
Stanford University)
- Yang He
(Baylor College of Medicine)
- Kévin Contrepois
(Stanford University School of Medicine
Stanford University
Stanford University)
- Hailan Liu
(Baylor College of Medicine)
- Joon T. Kim
(Stanford University School of Medicine
Stanford University)
- Amanda L. Wiggenhorn
(Stanford University School of Medicine
Stanford University
Stanford University)
- Julia T. Tanzo
(Stanford University School of Medicine
Stanford University)
- Alan Sheng-Hwa Tung
(Stanford University School of Medicine
Stanford University)
- Xuchao Lyu
(Stanford University School of Medicine
Stanford University
Stanford University)
- Peter-James H. Zushin
(University of California Berkeley)
- Robert S. Jansen
(Netherlands Cancer Institute
Radboud University)
- Basil Michael
(Stanford University School of Medicine)
- Kang Yong Loh
(Stanford University
Stanford University)
- Andrew C. Yang
(University of California San Francisco)
- Christian S. Carl
(University of Copenhagen)
- Christian T. Voldstedlund
(University of Copenhagen)
- Wei Wei
(Stanford University School of Medicine
Stanford University
Stanford University)
- Stephanie M. Terrell
(Stanford University School of Medicine
Stanford University)
- Benjamin C. Moeller
(University of California at Davis
University of California)
- Rick M. Arthur
(University of California)
- Gareth A. Wallis
(University of Birmingham)
- Koen Wetering
(Netherlands Cancer Institute
Thomas Jefferson University)
- Andreas Stahl
(University of California Berkeley)
- Bente Kiens
(University of Copenhagen)
- Erik A. Richter
(University of Copenhagen)
- Steven M. Banik
(Stanford University
Stanford University)
- Michael P. Snyder
(Stanford University School of Medicine
Stanford University
Stanford University
Stanford University)
- Yong Xu
(Baylor College of Medicine
Baylor College of Medicine)
- Jonathan Z. Long
(Stanford University School of Medicine
Stanford University
Stanford University
Stanford University)
Abstract
Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1–5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. 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.
Suggested Citation
Veronica L. Li & Yang He & Kévin Contrepois & Hailan Liu & Joon T. Kim & Amanda L. Wiggenhorn & Julia T. Tanzo & Alan Sheng-Hwa Tung & Xuchao Lyu & Peter-James H. Zushin & Robert S. Jansen & Basil Mic, 2022.
"An exercise-inducible metabolite that suppresses feeding and obesity,"
Nature, Nature, vol. 606(7915), pages 785-790, June.
Handle:
RePEc:nat:nature:v:606:y:2022:i:7915:d:10.1038_s41586-022-04828-5
DOI: 10.1038/s41586-022-04828-5
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Cited by:
- Zachary A. Graham & Jacob A. Siedlik & Carlos A. Toro & Lauren Harlow & Christopher P. Cardozo, 2023.
"Boldine Alters Serum Lipidomic Signatures after Acute Spinal Cord Transection in Male Mice,"
IJERPH, MDPI, vol. 20(16), pages 1-14, August.
- Dewen Liu & Shenghao Han & Chunyang Zhou, 2022.
"The Influence of Physical Exercise Frequency and Intensity on Individual Entrepreneurial Behavior: Evidence from China,"
IJERPH, MDPI, vol. 19(19), pages 1-22, September.
- Veronica L. Li & Shuke Xiao & Pascal Schlosser & Nora Scherer & Amanda L. Wiggenhorn & Jan Spaas & Alan Sheng-Hwa Tung & Edward D. Karoly & Anna Köttgen & Jonathan Z. Long, 2024.
"SLC17A1/3 transporters mediate renal excretion of Lac-Phe in mice and humans,"
Nature Communications, Nature, vol. 15(1), pages 1-10, December.
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