Le lactate du lactose, bon pour le cerveau ?

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Lactate Is Answerable for Brain Function and Treating Brain Diseases: Energy Substrates and Signal Molecule
Ming Cai Front. Nutr., 28 April 2022

Research to date has provided novel insights into lactate's positive role in multiple brain functions and several brain diseases. Although notable controversies and discrepancies remain, the neurobiological role and the metabolic mechanisms of brain lactate have now been described. A theoretical framework on the relevance between lactate and brain function and brain diseases is presented. This review begins with the source and route of lactate formation in the brain and food; goes on to uncover the regulatory effect of lactate on brain function; and progresses to gathering the application and concentration variation of lactate in several brain diseases (diabetic encephalopathy, Alzheimer's disease, stroke, traumatic brain injury, and epilepsy) treatment. Finally, the dual role of lactate in the brain is discussed. This review highlights the biological effect of lactate, especially L-lactate, in brain function and disease studies and amplifies our understanding of past research.

Introduction
Brain lactate, as a well-known metabolite, primarily roots in astrocytic glycolysis from blood glucose, glycogen, and blood lactate. Recently, the role of the “good guy” has gradually superseded the traditional concept of metabolic waste in medical literature in neuroscience (1). The most interesting dimension of this is the physiological character of lactate's role in mediating brain function (2). These canonical function involves learning and memory (3), cerebral blood flow (4), neurogenesis (5, 6) and cerebral microangiogenesis (7), energy metabolism (8), neuronal activity (9–11), and neuroprotection (12–15).

Therefore, lactate is competent to be a potential therapy for ameliorating the pathological process of some brain diseases associated with impaired brain function. In mammals, lactate exists as two enantiomers. The structure of asymmetrical C2 carbon leads to the two stereoisomers of lactate that are designated as L-lactate and D-lactate (16). L-lactate is the major enantiomer found in the brain and blood whereas D-lactate is normally present in very low concentrations under healthy physiological conditions (17). D-lactate is also considered as the rivalrous inhibitor of L-lactate since it competitively inhibits L-lactate transport (18). In different brain disease patterns, L- and D-lactate is reported to exert a similar or distinct effect on brain function. The involving mechanisms are far more complex than originally thought. For the most part, L-lactate can be utilized as a preferred energy substrate of neurons for meeting the energy demand (19, 20) or act as the novel hormone-like effect called lactormone (21, 22). But current research about D-lactate's role in brain function and brain-related disease is sparse and debatable. D-lactate-mediated mechanisms are also unclear.

In this narrative review, we aim to provide a comprehensive and profound summary of the role of lactate in brain function and related diseases. Consequently, we expound the food source of lactate intake, discuss the lactate enantiomers and their metabolism manner in the brain, compare the influence of L- and D-lactate on brain functions, expound on the effect of L- and D-lactate replenishment on several common brain diseases, and summarize the mechanisms of L-lactate.

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Lactate Intakes From the Food

Lactate, as the predominant end-product of lactose fermentation in the food (68), is produced by the lactic acid bacteria, namely, gram-positive and catalase-negative microorganisms. Such microorganisms are involved in the fermentation of a range of foods and beverages, such as dairy products, meat, fish, vegetable, sourdough, wine, and cider (68), which creates the specific flavors and aromas for the food and benefits human health (69). People can uptake lactate from cheese, yogurt, wine, fermented vegetables (69), and fermented oyster extract (70). Thereby, lactate will appear in the gut via the consumption of fermented foods. In addition, prebiotic, fiber-containing foods also are the way of the lactate intake, such as broccoli, brussels sprouts, cabbage, cauliflower, collard greens, kale, radish, and rutabaga (37). Since gut microbiota is likely to produce a racemic mixture, it is not surprising that L- and D-lactate are generated simultaneously following the above food intake (37).

The disposal of lactate in the lower gut can be converted to acetate, butyrate, propionate, and succinate. Alternatively, the unverified idea of “gut-soma lactate shuttle” is another way for the disposal of lactate in the gut, in which the lactate production in the gut releases into the systemic circulation (37). The discovery of the sodium-dependent monocarboxylate transporter (SMCT) (including SMCT1 and SMCT2) is favorable evidence for supporting this hypothesis, which is located in the mouse digestive tract and involved in the transport of food-derived monocarboxylates, such as lactate (71). The other implicit clue is the phenomenon of the rise in the blood L-lactate after a carbohydrate diet (37, 72). Tappy's team finds that dietary fructose or the co-mixture (fructose and glucose) facilitate the L-lactate release into the systemic circulation (73, 74).

Furthermore, glucose rooted in the oxidation of carbohydrate only provides 10–20% energy, while other carbohydrate energy sources like glycogen and L-lactate accounts for 70–80% in the condition of exercise (75). That is to say when blood glucose is supported by hepatic glycogenolysis and gluconeogenesis, L-lactate plays important role in carbohydrate energy substrate distribution (72). As blood L-lactate can be transported into the brain via the MCT1 (32, 33), net L-lactate uptake directly provides 12% of brain fuel (37, 75, 76). Besides, gluconeogenesis provides 45% of brain fuel. Thereby, L-lactate comprises 57% of the total brain energy source (75). Regarding D-lactate, it can be excreted in urine by renal (64) or feces by gut (37) and cannot be detected in the blood under normal physiological conditions (64). Its excessive accumulation can result in acidosis and irritation of the lower bowel. Furthermore, the release of D-lactate into circulation also cause neurotoxic effect (37). The clinical presentation of D-lactic acidosis is characterized by episodes of encephalopathy and metabolic acidosis (24).

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Traduction de l'étude

Apports en lactate de la nourriture

Le lactate, en tant que produit final prédominant de la fermentation du lactose dans les aliments (68), est produit par les bactéries lactiques, à savoir les micro-organismes gram-positifs et catalase-négatifs. Ces micro-organismes sont impliqués dans la fermentation d'une gamme d'aliments et de boissons, tels que les produits laitiers, la viande, le poisson, les légumes, le levain, le vin et le cidre (68), ce qui crée les saveurs et les arômes spécifiques des aliments et profite à la santé humaine. (69). Les gens peuvent absorber le lactate du fromage, du yaourt, du vin, des légumes fermentés (69) et de l'extrait d'huître fermenté (70). Ainsi, le lactate apparaîtra dans l'intestin via la consommation d'aliments fermentés. De plus, les aliments prébiotiques contenant des fibres sont également la voie de l'apport en lactate, comme le brocoli, les choux de Bruxelles, le chou, le chou-fleur, le chou vert, le chou frisé, le radis et le rutabaga (37). Étant donné que le microbiote intestinal est susceptible de produire un mélange racémique, il n'est pas surprenant que le L- et le D-lactate soient générés simultanément après l'apport alimentaire ci-dessus (37).

L'élimination du lactate dans l'intestin inférieur peut être convertie en acétate, butyrate, propionate et succinate. Alternativement, l'idée non vérifiée de «navette intestin-soma lactate» est un autre moyen d'éliminer le lactate dans l'intestin, dans lequel la production de lactate dans l'intestin se libère dans la circulation systémique (37). La découverte du transporteur de monocarboxylates dépendant du sodium (SMCT) (comprenant SMCT1 et SMCT2) est une preuve favorable à l'appui de cette hypothèse, qui est localisé dans le tube digestif de la souris et impliqué dans le transport des monocarboxylates d'origine alimentaire, comme le lactate (71 ). L'autre indice implicite est le phénomène de remontée du L-lactate sanguin après un régime glucidique (37, 72). L'équipe de Tappy constate que le fructose alimentaire ou le co-mélange (fructose et glucose) facilite la libération de L-lactate dans la circulation systémique (73, 74).

De plus, le glucose enraciné dans l'oxydation des glucides ne fournit que 10 à 20% d'énergie, tandis que d'autres sources d'énergie glucidiques comme le glycogène et le L-lactate représentent 70 à 80% dans des conditions d'exercice (75). C'est-à-dire que lorsque la glycémie est soutenue par la glycogénolyse hépatique et la gluconéogenèse, le L-lactate joue un rôle important dans la distribution du substrat énergétique glucidique (72). Comme le L-lactate sanguin peut être transporté dans le cerveau via le MCT1 (32, 33), l'absorption nette de L-lactate fournit directement 12 % du carburant cérébral (37, 75, 76). De plus, la gluconéogenèse fournit 45% du carburant cérébral. Ainsi, le L-lactate représente 57 % de la source totale d'énergie cérébrale (75). Quant au D-lactate, il peut être excrété dans les urines par les reins (64) ou les fèces par les intestins (37) et ne peut pas être détecté dans le sang dans des conditions physiologiques normales (64). Son accumulation excessive peut entraîner une acidose et une irritation de la partie inférieure de l'intestin. De plus, la libération de D-lactate dans la circulation provoque également un effet neurotoxique (37). La présentation clinique de l'acidose D-lactique est caractérisée par des épisodes d'encéphalopathie et d'acidose métabolique (24)