The Science and Translation of Lactate Shuttle Theory
Open accessAbstract
Once thought to be a waste product of anaerobic metabolism, lactate is now known to form continuously under aerobic conditions. Shuttling between producer and consumer cells fulfills at least three purposes for lactate: (1) a major energy source, (2) the major gluconeogenic precursor, and (3) a signaling molecule. "Lactate shuttle" (LS) concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signaling. In medicine, it has long been recognized that the elevation of blood lactate correlates with illness or injury severity. However, with lactate shuttle theory in mind, some clinicians are now appreciating lactatemia as a "strain" and not a "stress" biomarker. In fact, clinical studies are utilizing lactate to treat pro-inflammatory conditions and to deliver optimal fuel for working muscles in sports medicine. The above, as well as historic and recent studies of lactate metabolism and shuttling, are discussed in the following review.
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Lactate can indirectly contribute to hepatic glycogen synthesis.
“Finally, lactate can also indirectly contribute to hepatic glycogen synthesis (Brooks, 2018).”
From Fructose co‐ingestion to increase carbohydrate availability in athletes (2019) · cites this paper as Brooks, 2018
Lactate is a linker between glycolysis and oxidative metabolism that plays roles as an energy source, gluconeogenic precursor and signalling molecule by shuttling among cells, tissues and organs.
“Lactate was once considered a waste product of anaerobic metabolism, but the prevailing view now agrees that it is a linker between glycolysis and oxidative metabolism that plays the role of an energy source, gluconeogenic precursor and signalling molecule by shuttling among cells, tissues and organs [11–13].”
Astrocytes obtain their energy predominantly from glycolysis.
“In contrast to neurons, astrocytes obtain their energy predominantly from glycolysis (Brooks, 2018).”
From Toxic Concentrations of Glutamate Induce Ferroptosis without Affecting Mitochondrial Respiration in Rodent Brain Slice Cultures (2026) · cites this paper as Brooks, 2018
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References 337 · Cited by 1,486
- Authors
- Brooks, G. A.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Brooks, George A.
- ORCID
- Brooks, George A.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 27
- Issue
- 4
- Pages
- 757-785
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2795504602
- Cited by
- 1,486
- References
- 337
- Citations by year
- 2026: 304 · 2025: 283 · 2024: 206 · 2023: 197 · 2022: 150 · 2021: 138 · 2020: 129 · 2019: 55 · 2018: 24
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Pac-12 Conference (#3-02-Brooks-17)
- UCB
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Keywords
- lactate metabolism, gluconeogenesis, signal transduction, lactatemia, muscle energy metabolism
- MeSH terms
- Animals, Brain, Gluconeogenesis, Glycolysis, Humans, Oxidation-Reduction, Lactic Acid
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