Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?

Ma, Lina; Huang, Xiao-Bo; Muyayalo, Kahindo P; Mor, Gil; Liao, Aihua

doi:10.3389/fimmu.2020.00279

Cited by 67 publications

(60 citation statements)

References 109 publications

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“…HIF-1α activity is mainly regulated by protein stability, with ubiquitination and subsequent degradation occurring rapidly in states of normoxia [30,31]. In addition, lactate levels are relatively high in the fetus (~0.5-2 mM in umbilical venous blood at 17-21 weeks gestation [32]) due to high glycolytic activity of the placenta [33], which decreases rapidly after birth (~0.5-1 mM in umbilical venous blood at term delivery [32]) after achieving independence from placental circulation, with maternal arterial lactate levels of 0.68 ± 0.07 mM at delivery [34]. Lactate can also stabilize HIF-1α in fibroblasts [35] and cancer cells Metabolic sensors and mitochondria.…”

Section: Spontaneous Breathingmentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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Current methods to differentiate cardiomyocytes from human pluripotent stem cells (PSCs) inadequately recapitulate complete development and result in PSC-derived cardiomyocytes (PSC-CMs) with an immature or fetal-like phenotype. Embryonic and fetal development are highly dynamic periods during which the developing embryo or fetus is exposed to changing nutrient, oxygen, and hormone levels until birth. It is becoming increasingly apparent that these metabolic changes initiate developmental processes to mature cardiomyocytes. Mitochondria are central to these changes, responding to these metabolic changes and transitioning from small, fragmented mitochondria to large organelles capable of producing enough ATP to support the contractile function of the heart. These changes in mitochondria may not simply be a response to cardiomyocyte maturation; the metabolic signals that occur throughout development may actually be central to the maturation process in cardiomyocytes. Here, we review methods to enhance maturation of PSC-CMs and highlight evidence from development indicating the key roles that mitochondria play during cardiomyocyte maturation. We evaluate metabolic transitions that occur during development and how these affect molecular nutrient sensors, discuss how regulation of nutrient sensing pathways affect mitochondrial dynamics and function, and explore how changes in mitochondrial function can affect metabolite production, the cell cycle, and epigenetics to influence maturation of cardiomyocytes.

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Section: Spontaneous Breathingmentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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“…4. Blastocysts, placenta, trophoblasts and decidual immune cells also produce substantial amounts of lactate [36]. 5.…”

Section: Secondary Glucose Cycling (Figs 5 and 6)mentioning

confidence: 99%

The anabolic role of the Warburg, Cori-cycle and Crabtree effects in health and disease

Soeters¹,

Shenkin

Sobótka

et al. 2021

Clinical Nutrition

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In evolution, genes survived that could code for metabolic pathways, promoting long term survival during famines or fasting when suffering from trauma, disease or during physiological growth. This requires utilization of substrates, already present in some form in the body. Carbohydrate stores are limited and to survive long, their utilization is restricted to survival pathways, by inhibiting glucose oxidation and glycogen synthesis. This leads to insulin resistance and spares muscle protein, because being the main supplier of carbon for new glucose production.In these survival pathways, part of the glucose is degraded in glycolysis in peripheral (muscle) tissues to pyruvate and lactate (Warburg effect), which are partly reutilized for glucose formation in liver and kidney, completing the Cori-cycle. Another part of the glucose taken up by muscle contributes, together with muscle derived amino acids, to the production of substrates consisting of a complete amino acid mix but extra non-essential amino acids like glutamine, alanine, glycine and proline. These support cell proliferation, matrix deposition and redox regulation in tissues, specifically active in host response and during growth.In these tissues, also glucose is taken up delivering glycolytic intermediates, that branch off and act as building blocks and produce reducing equivalents. Lactate is also produced and released in the circulation, adding to the lactate released by muscle in the Cori-cycle and completing secondary glucose cycles.Increased fluxes through these cycles lead to modest hyperglycemia and hyperlactatemia in states of healthy growth and disease and are often misinterpreted as induced by hypoxia.

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“…The lactate concentration can transitorily increase to 15 mM during exercise in humans, while it is usually 1-3 mM at rest. During embryonic development, blastocysts consume approximately 50 to 320 pmol of glucose/embryo/h, and 90% of the consumed glucose is converted to lactate (10). Lactate has the highest circulatory turnover of all metabolites and exceeds that of glucose in mice by 1.1-fold during the fed state and 2.5-fold during the fasted state, as demonstrated by 13 C-labeled nutrients with intravenous infusions (21).…”

Section: Lactate Turnovermentioning

confidence: 99%

“…5) The physiological level of the intracellular pH in tumor cells is controlled by lactate outflux with H + cotransports via upregulation of MCTs, driving the formation of an acidic tumor microenvironment (10).…”

Section: Lactate In the Tumor Microenvironmentmentioning

confidence: 99%

Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects

et al. 2021

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Lactate is an end product of glycolysis. As a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule. We briefly summarize emerging concepts regarding lactate metabolism, such as the lactate shuttle, lactate homeostasis, and lactate-microenvironment interaction. Accumulating evidence indicates that lactate-mediated reprogramming of immune cells and enhancement of cellular plasticity contribute to establishing disease-specific immunity status. However, the mechanisms by which changes in lactate states influence the establishment of diverse functional adaptive states are largely uncharacterized. Posttranslational histone modifications create a code that functions as a key sensor of metabolism and are responsible for transducing metabolic changes into stable gene expression patterns. In this review, we describe the recent advances in a novel lactate-induced histone modification, histone lysine lactylation. These observations support the idea that epigenetic reprogramming-linked lactate input is related to disease state outputs, such as cancer progression and drug resistance.

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Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?

Cited by 67 publications

References 109 publications

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

The anabolic role of the Warburg, Cori-cycle and Crabtree effects in health and disease

Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects

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