Brain lactate metabolism: the discoveries and the controversies

Dienel, Gerald A

doi:10.1038/jcbfm.2011.175

Cited by 479Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismAdvanced MRI Techniques and Applications

Brain lactate metabolism: the discoveries and the controversies

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Dienel, Gerald A·2012·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1038/jcbfm.2011.175PMC PMC3390802

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Abstract

Potential roles for lactate in the energetics of brain activation have changed radically during the past three decades, shifting from waste product to supplemental fuel and signaling molecule. Current models for lactate transport and metabolism involving cellular responses to excitatory neurotransmission are highly debated, owing, in part, to discordant results obtained in different experimental systems and conditions. Major conclusions drawn from tabular data summarizing results obtained in many laboratories are as follows: Glutamate-stimulated glycolysis is not an inherent property of all astrocyte cultures. Synaptosomes from the adult brain and many preparations of cultured neurons have high capacities to increase glucose transport, glycolysis, and glucose-supported respiration, and pathway rates are stimulated by glutamate and compounds that enhance metabolic demand. Lactate accumulation in activated tissue is a minor fraction of glucose metabolized and does not reflect pathway fluxes. Brain activation in subjects with low plasma lactate causes outward, brain-to-blood lactate gradients, and lactate is quickly released in substantial amounts. Lactate utilization by the adult brain increases during lactate infusions and strenuous exercise that markedly increase blood lactate levels. Lactate can be an 'opportunistic', glucose-sparing substrate when present in high amounts, but most evidence supports glucose as the major fuel for normal, activated brain.

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Lactate can also be from other sources, such as glutamine.
“However, lactate can also be from other sources, such as glutamine [52,53].”
From Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation (2023) · cites this paper as [53]
Both LDH isoforms are rapidly equilibrative.
“however, both isoforms are rapidly equilibrative (as argued by Gandhi et al., 2009; Dienel, 2012; Hertz et al., 2014; Bak and Schousboe, 2017)”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Dienel, 2012
The ultimate fate of the exported lactate may be a combination of "catch-up" oxidation by many neighboring brain cells (and by the stimulated neurons themselves) as well as some net lactate excretion from the brain, particularly when activation is strong and synchronous, as in epilepsy.
“of “catch-up” oxidation by many neighboring brain cells (and by the stimulated neurons themselves) as well as some net lactate excretion from the brain (Dienel, 2012; Glenn et al., 2015), particularly when activation is strong and synchronous, as in epilepsy (Collins et al., 1970; During et al., 1994)”
From Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake (2017) · cites this paper as Dienel, 2012

THE [ 14 C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1
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Authors: Dienel, G. A.
Affiliations: University of Arkansas for Medical Sciences (US)
Corresponding author: Dienel, Gerald A
ORCID: Dienel, Gerald A
Venue: Journal of Cerebral Blood Flow & Metabolism
Publisher: SAGE Publications
Published: 2011-12-21
Volume: 32
Issue: 7
Pages: 1107-1138
ISSN: 0271-678X (ISSN-L)
1559-7016
DOI: 10.1038/jcbfm.2011.175
PMC: PMC3390802
OpenAlex: W2032163981
Cited by: 479
References: 242
Citations by year: 2026: 18 · 2025: 28 · 2024: 29 · 2023: 30 · 2022: 35 · 2021: 26 · 2020: 28 · 2019: 39 · 2018: 38 · 2017: 53 · 2016: 32 · 2015: 45 · 2014: 36 · 2013: 24 · 2012: 18
FWCI: 2.32
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK081936, R01DK081936)
National Institute of Neurological Disorders and Stroke (NS038230, R01NS038230, R56NS038230)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords: lactate transport, brain energy metabolism, synaptosomes, glucose transport, lactate utilization, physical activity, lactate signaling
MeSH terms: Animals, Brain, Energy Metabolism, Humans, Lactic Acid

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Brain lactate metabolism: the discoveries and the controversies

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