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. 2023 May 12:17:1144639.
doi: 10.3389/fnins.2023.1144639. eCollection 2023.

Lactate shuttling as an allostatic means of thermoregulation in the brain

Daniel A Kane  1 , Alexander C Y Foo  2 , Erin B Noftall  1 , Karen Brebner  3 , D Gerrard Marangoni  2
Affiliations

Lactate shuttling as an allostatic means of thermoregulation in the brain

Daniel A Kane et al. Front Neurosci. .

Abstract

Lactate, the redox-balanced end product of glycolysis, travels within and between cells to fulfill an array of physiologic functions. While evidence for the centrality of this lactate shuttling in mammalian metabolism continues to mount, its application to physical bioenergetics remains underexplored. Lactate represents a metabolic "cul-de-sac," as it can only re-enter metabolism by first being converted back to pyruvate by lactate dehydrogenase (LDH). Given the differential distribution of lactate producing/consuming tissues during metabolic stresses (e.g., exercise), we hypothesize that lactate shuttling vis-à-vis the exchange of extracellular lactate between tissues serves a thermoregulatory function, i.e., an allostatic strategy to mitigate the consequences of elevated metabolic heat. To explore this idea, the rates of heat and respiratory oxygen consumption in saponin-permeabilized rat cortical brain samples fed lactate or pyruvate were measured. Heat and respiratory oxygen consumption rates, and calorespirometric ratios were lower during lactate vs. pyruvate-linked respiration. These results support the hypothesis of allostatic thermoregulation in the brain with lactate.

Keywords: bioenergetics; brain; calorimetry; lactate; mitochondria; pyruvate; thermal physiology.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Hypothetical model in which the lactate shuttle serves a thermoregulatory function in mammals. In the example depicted (mouse), excess lactate (La−) released by skeletal muscle during periods of elevated glycolysis (e.g., exercise) is shuttled to the brain via circulating blood. In the model, metabolism of La− of extracellular origin is accompanied by a lower rate of heat production. Figure created with BioRender.com.
Figure 2
Figure 2
Representative traces of (A) heat rate (dQ/dt), (B) oxygen consumption rate (JO2) and (C) calorespirometric (CR) ratio in permeabilized rat frontal cortex samples fed pyruvate or lactate + NAD+. Numeric values are mean ± SEM; n = 3; *p-values from t-tests with 6 independent trials.
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