Energy Contribution of Octanoate to Intact Rat Brain Metabolism Measured by 13 C Nuclear Magnetic Resonance Spectroscopy
Open accessAbstract
Glucose is the dominant oxidative fuel for brain, but studies have indicated that fatty acids are used by brain as well. We postulated that fatty acid oxidation in brain could contribute significantly to overall energy usage and account for non-glucose-derived energy production. [2,4,6,8- 13 C 4 ]octanoate oxidation in intact rats was determined by nuclear magnetic resonance spectroscopy. We found that oxidation of 13 C-octanoate in brain is avid and contributes ∼20% to total brain oxidative energy production. Labeling patterns of glutamate and glutamine were distinct, and analysis of these metabolites indicated compartmentalized oxidation of octanoate in brain. Examination of liver and blood spectra revealed that label from 13 C-octanoate was incorporated into glucose and ketones, which enabled calculation of its overall energy contribution to brain metabolism: glucose (predominantly unlabeled) and 13 C-labeled octanoate can account for the entire oxidative metabolism of brain. Additionally, flux through anaplerotic pathways relative to tricarboxylic acid cycle flux ( Y ) was calculated to be 0.08 ± 0.039 in brain, indicating that anaplerotic flux is significant and should be considered when assessing brain metabolism. Y was associated with the glutamine synthesis compartment, consistent with the view that anaplerotic flux occurs primarily in astrocytes.
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
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?
Fatty acid oxidation, predominantly in astrocytes, contributes approximately 20% of total brain energy supply.
“FA oxidation—predominantly in astrocytes—contributes ~20% of total brain energy supply (Ebert et al., 2003).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Ebert et al., 2003
The Discussion reports that octanoate contributed approximately 20% of brain oxidative energy in intact rats and says the data support its oxidation in astrocytes. The claim generalizes that result to fatty acid oxidation and total brain energy supply without specifying the octanoate-infusion condition or rat population. (LLM, conf=0.88)
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.
Cites
Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids
Oldendorf, W. (1973) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1973.224.6.1450 · Cited by 463 · cited 5× · see citing works
“The higher proportion may be explained by differences in transport rates and mechanisms of the two substrates (Oldendorf, 1971, 1973), or it could be a consequence of anesthesia, fasting, or species differences.”
BackgroundInfluential
Flagged first, then by citations
Cited by
Sorted by citations
Acetate is a bioenergetic substrate for human glioblastoma and brain metastases
Mashimo, T., Pichumani, K., Vemireddy, V., Hatanpaa, K. J., Singh, D. K., Sirasanagandla, S., Nannepaga, S., Piccirillo, S. G., Kovacs, Z., Foong, C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.025 · Cited by 760 · see citing works
Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism
Poitelon, Y., Kopec, A. M., & Belin, S. (2020) · Cells · doi:10.3390/cells9040812 · Cited by 394 · see citing works
ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism
Qi, G., Mi, Y., Shi, X., Gu, H., Brinton, R. D., & Yin, F. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108572 · Cited by 379 · see citing works
Brain lipidomics: From functional landscape to clinical significance
Yoon, J. H., Seo, Y., Jo, Y. S., Lee, S., Cho, E., Cazenave-Gassiot, A., Shin, Y.-S., Moon, M. H., An, H. J., Wenk, M. R., et al. (2022) · Science Advances · doi:10.1126/sciadv.adc9317 · Cited by 324 · see citing works
Beyond the GFAP-Astrocyte Protein Markers in the Brain
Jurga, A. M., Paleczna, M., Kadluczka, J., & Kuter, K. Z. (2021) · Biomolecules · doi:10.3390/biom11091361 · Cited by 319 · see citing works
Regulation of Ketone Body Metabolism and the Role of PPARα
Grabacka, M., Pierzchalska, M., Dean, M., & Reiss, K. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122093 · Cited by 305 · see citing works
Fanning, S., Haque, A., Imberdis, T., Baru, V., Barrasa, M. I., Nuber, S., Termine, D., Ramalingam, N., Ho, G. P. H., Noble, T., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.11.028 · Cited by 285 · see citing works
Ota, M., Matsuo, J., Ishida, I., Takano, H., Yokoi, Y., Hori, H., Yoshida, S., Ashida, K., Nakamura, K., Takahashi, T., et al. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2018.10.048 · Cited by 276 · see citing works
Lipid and Lipoprotein Metabolism in Microglia
Loving, B. A., & Bruce, K. D. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00393 · Cited by 255 · see citing works
Cunnane, S. C., Courchesne‐Loyer, A., St‐Pierre, V., Vandenberghe, C., Pierotti, T., Fortier, M., Croteau, E., & Castellano, C. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12999 · Cited by 250 · see citing works
Microglia reprogram metabolic profiles for phenotype and function changes in central nervous system
Yang, S., Qin, C., Hu, Z.-W., Zhou, L.-Q., Yu, H.-H., Chen, M., Bosco, D. B., Wang, W., Wu, L.-J., & Tian, D.-S. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105290 · Cited by 232 · see citing works
The energetic brain—A review from students to students
Bordone, M. P., Salman, M. M., Titus, H. E., Amini, E., Andersen, J. V., Chakraborti, B., Diuba, A. V., Dubouskaya, T. G., Ehrke, E., Espindola de Freitas, A., et al. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14829 · Cited by 205 · see citing works
Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases
Yang, D., Wang, X., Zhang, L., Fang, Y., Zheng, Q., Liu, X., Yu, W., Chen, S., Ying, J., & Hua, F. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00828-0 · Cited by 179 · see citing works
Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation
Farmer, B., Kluemper, J., & Johnson, L. (2019) · Cells · doi:10.3390/cells8020182 · Cited by 164 · see citing works
Cerebral Metabolic Changes During Sleep
Aalling, N. N., Nedergaard, M., & DiNuzzo, M. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0868-9 · Cited by 101 · see citing works
Duarte, J. M. N., Lanz, B., & Gruetter, R. (2011) · Frontiers in Neuroenergetics · doi:10.3389/fnene.2011.00003 · Cited by 82 · see citing works
Calì, C., Cantando, I., Veloz Castillo, M. F., Gonzalez, L., & Bezzi, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168922 · Cited by 66 · see citing works
Sawicka-Gutaj, N., Zawalna, N., Gut, P., & Ruchała, M. (2022) · Pharmacological Reports · doi:10.1007/s43440-022-00377-w · Cited by 57 · see citing works
Area-Gomez, E., Larrea, D., Pera, M., Agrawal, R. R., Guilfoyle, D. N., Pirhaji, L., Shannon, K., Arain, H. A., Ashok, A., Chen, Q., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-61142-8 · Cited by 55 · see citing works
How expensive is the astrocyte?
Barros, L. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x221077343 · Cited by 51 · see citing works
- Authors
- Ebert, D., Haller, R. G., & Walton, M. E.
- Affiliations
- Texas Health Dallas (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-07-02
- Volume
- 23
- Issue
- 13
- Pages
- 5928-5935
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6741266
- OpenAlex
- W2126068729
- Cited by
- 427
- References
- 1
- Citations by year
- 2026: 19 · 2025: 40 · 2024: 48 · 2023: 34 · 2022: 35 · 2021: 31 · 2020: 34 · 2019: 25 · 2018: 20 · 2017: 19 · 2016: 26 · 2015: 14 · 2014: 16 · 2013: 9 · 2012: 9
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- U.S. Department of Veterans Affairs
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- octanoate, fatty acid oxidation, brain energy metabolism, 13C-labeled fatty acids, glutamate, glutamine, TCA cycle, astrocytes, ketone bodies, glucose metabolism, rat brain
- MeSH terms
- Animals, Aspartic Acid, Brain, Brain Chemistry, Caprylates, Carbon Isotopes, Energy Metabolism, Glucose, Glutamine, Ketones, Liver, Male, Models, Biological, Magnetic Resonance Spectroscopy, Rats, Sprague-Dawley, Glutamic Acid, Rats
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