Preferential lactate metabolism in the human brain during exogenous and endogenous hyperlactataemia
Bibliographic record
Abstract
Abstract At rest, glucose serves as the brain's primary oxidative substrate; however, when circulating lactate is elevated, lactate oxidation increases. Whether this glucose‐sparing effect differs when lactate is elevated via passive infusion versus exercise remains unknown. To address this, 13 healthy adults (six females) completed protocols of: (1) intravenous sodium lactate infusion (exogenous hyperlactataemia); and (2) cycling exercise (endogenous hyperlactataemia) to matched elevations in arterial lactate concentration (∼4 and ∼8 mmol/l). Radial arterial and internal jugular venous sampling and measures of cerebral blood flow (CBF) were used to calculate cerebral metabolic rates of glucose (CMR Glc ), lactate (CMR iLac ), and oxygen (). The exogenous infusion protocol resulted in a higher CBF compared to exercise ( P < 0.001), despite causing systemic alkalosis ( P < 0.001). During both protocols remained unchanged across increases in lactate concentrations ( P = 0.610), while CMR Glc decreased (lactate, P = 0.009; condition, P = 0.373) and CMR iLac increased in a dose‐dependent manner (lactate, P < 0.001; condition, P = 0.972). At an arterial concentration of 8 mmol/l, circulating lactate accounted for 24% of total cerebral oxidative metabolism. Elevated circulating lactate leads to preferential lactate oxidation and reduced glucose utilization, irrespective of whether lactate is delivered exogenously or produced endogenously. image Key points The human brain relies primarily on oxidative glucose metabolism; however, with age and in many pathologies cerebral glucose metabolism declines; therefore, there is interest in investigating alternative fuel sources that can meet the high energetic needs of the brain. The present study investigates whether increased lactate availability exerts a glucose‐sparing effect in the healthy human brain, and whether this effect is consistent across physiologically distinct states of exogenous (sodium lactate infusion) and endogenous (exercise‐induced) hyperlactataemia. We assessed cerebral uptake and metabolism of glucose and lactate following exercise and lactate infusion, using simultaneous arterial and jugular venous blood samples, and Duplex ultrasound. Despite stark systemic physiological differences between conditions, cerebral glucose metabolism declined in proportion to increased circulating lactate irrespective of whether it is delivered exogenously or produced endogenously. These data provide clear evidence that lactate is preferentially oxidized by the brain when made available, helping preserve glucose for non‐energetic roles.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".