Lactic Acid: No Longer an Inert and End-Product of Glycolysis

Sun, Shan; Li, Heng; Chen, Jianghua; Qian, Qi

doi:10.1152/physiol.00016.2017

Cited by 212 publications

(190 citation statements)

References 156 publications

(172 reference statements)

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“…The lactate, which was also increased in the cecum of the KHK-F mice, may stimulate Nts expression in GLUTag cells. Thus, it might be the regulatory component activating Nts expression in the cecum of the KHK-F. Lactate signals though the G-protein-coupled receptor GPR81 (58) or is transported into intestinal cells by the monocarboxylate transporters (59). Expression of GPR81 in the intestine is not well documented (60).…”

Section: Discussionmentioning

confidence: 99%

Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism

et al. 2019

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Current fructose consumption levels often overwhelm the intestinal capacity to absorb fructose. We investigated the impact of fructose malabsorption on intestinal endocrine function and addressed the role of the microbiota in this process. To answer this question, a mouse model of moderate fructose malabsorption [ketohexokinase mutant (KHK)−/−] and wild‐type (WT) littermate mice were used and received a 20%‐fructose (KHK‐F and WT‐F) or 20%‐glucose diet. Cholecystokinin (Cck) mRNA and protein expression in the ileum and cecum, as well as preproglucagon (Gcg) and neurotensin (Nts) mRNA expression in the cecum, increased in KHK‐F mice. In KHK‐F mice, triple‐label immunohistochemistry showed major up‐regulation of CCK in enteroendocrine cells (EECs) that were glucagon‐like peptide‐1 (GLP‐1)+/Peptide YY (PYY−) in the ileum and colon and GLP‐1−/PYY− in the cecum. The cecal microbiota composition was drastically modified in the KHK‐F in association with an increase in glucose, propionate, succinate, and lactate concentrations. Antibiotic treatment abolished fructose malabsorption‐dependent induction of cecal Cck mRNA expression and, in mouse GLUTag and human NCI‐H716 cells, Cck mRNA expression levels increased in response to propionate, both suggesting a microbiota‐dependent process. Fructose reaching the lower intestine can modify the composition and metabolism of the microbiota, thereby stimulating the production of CCK from the EECs possibly in response to propionate.—Zhang, X., Grosfeld, A., Williams, E., Vasiliauskas, D., Barretto, S., Smith, L., Mariadassou, M., Philippe, C., Devime, F., Melchior, C., Gourcerol, G., Dourmap, N., Lapaque, N., Larraufie, P., Blottière, H. M., Herberden, C., Gerard, P., Rehfeld, J. F., Ferraris, R. P., Fritton, J. C., Ellero‐Simatos, S., Douard, V. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism. FASEB J. 33, 7126–7142 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism

et al. 2019

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“…48,49 Wound healing is a complex and tightly regulated inflammatory process, during which excessive inflammation leads to greater scaring. [59][60][61] High expression of TGF-β leads to excess fibroblast activity, which contributes to the development of hypertrophic scars and keloids. 51 closer, respectively, to healthy skin than that of Tegaderm.…”

Section: Discussionmentioning

confidence: 99%

“…57,58 Revascularization could be stimulated by the lactic acid supplied by the biodegradable PLGA scaffold, which has been shown to increase angiogenesis. [59][60][61] High expression of TGF-β leads to excess fibroblast activity, which contributes to the development of hypertrophic scars and keloids. The composition of collagen subtypes can also give insight into the degree of scarring that may ultimately develop in the wounds.…”

Section: Discussionmentioning

confidence: 99%

Sprayable and biodegradable, intrinsically adhesive wound dressing with antimicrobial properties

Daristotle

Lau

Erdi

et al. 2019

Bioengineering & Transla Med

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Conventional wound dressings are difficult to apply to large total body surface area (TBSA) wounds, as they typically are prefabricated, require a layer of adhesive coating for fixation, and need frequent replacement for entrapped exudate. Large TBSA wounds as well as orthopedic trauma and low-resource surgery also have a high risk of infection. In this report, a sprayable and intrinsically adhesive wound dressing loaded with antimicrobial silver is investigated that provides personalized fabrication with minimal patient contact. The dressing is composed of adhesive and biodegradable poly(lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA/PEG) blend fibers with or without silver salt (AgNO 3 ). in vitro studies demonstrate that the PLGA/PEG/Ag dressing has antimicrobial properties and low cytotoxicity, with antimicrobial silver controllably released over 7-14 days. In a porcine partial-thickness wound model, the wounds treated with both antimicrobial and nonantimicrobial PLGA/PEG dressings heal at rates similar to those of the clinical, thin film polyurethane wound dressing, with similar scarring. However, PLGA/PEG adds a number of features beneficial for wound healing: greater exudate absorption, integration into the wound, a 25% reduction in dressing changes, and tissue regeneration with greater vascularization. There is also modest improvement in epidermis thickness compared to the control wound dressing. K E Y W O R D Santimicrobial wound dressings, biodegradable polymers, silver, solution blow spinning, wound healing

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“…Numerous studies have confirmed that glycolysis intermediate can rapidly meet the energy requirement for cell proliferation, the material needs for fatty acids and nucleotides [9] . The glycolysis products, lactic acid also plays multiple roles in cancer processes, including energy regulation, immune tolerance, wound healing, cancer growth and metastasis [10,11] . These studies have established that glycolysis can provide favorable conditions for tumor proliferation and thus plays a pivotal role in cancer development.…”

Section: Introductionmentioning

confidence: 99%

Persistent cell proliferation signals correlates with increased glycolysis in tumor hypoxia microenvironment across cancer types

Wei

Huang

et al. 2020

Preprint

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Background：Altered metabolism is a hallmark of cancer and glycolysis is one of the important factors promoting tumor development. Given that the absence of multi-sample big data research about glycolysis, the molecular mechanisms involved in glycolysis or the relationships between glycolysis and tumor microenvironment are not fully studied. Thus, a more comprehensive approach in a pan-cancer landscape may be needed.Methods: Here, we develop a computational pipeline to study multi-omics molecular features defining glycolysis activity and identify molecular alterations that correlate with glycolysis.We apply a 22-gene expression signature to define the glycolysis activity landscape and verify the robustness using clinically defined glycolysis samples from several previous studies. Based on gene expression signature, we classify about 5552 of 9229 tumor samples into glycolysis score-high and score-low groups across 25 cancer types from The Cancer Genome Atlas (TCGA) and demonstrate their prognostic associations. Moreover, using genomes and transcriptome data, we characterize the association of copy-number aberrations (CNAs), somatic single-nucleotide variants (SNVs) and hypoxia signature with glycolysis activity.Findings: Gene set variation analysis (GSVA) score by gene set expression was verified robustly to represent glycolytic activity and highly glycolytic tumors presented a poor overall survival in some cancer types. Then, we identified various types of molecular features promoting tumor cell proliferation were associated with glycolysis activity. Our study showed that TCA cycle and respiration electron transport were active in glycolysis-high tumors, indicating glycolysis was not a symptom of impaired oxidative metabolism. The glycolytic score significantly correlated with hypoxia score across all 3 cancer types. Glycolysis score was also associated with elevated genomic instability. In all tumor types, high glycolysis tumors exhibited characteristic driver genes altered by CNAs identified multiple oncogenes and tumor suppressors. We observed widespread glycolysis-associated dysregulation of mRNA across cancers and screened out HSPA8 and P4HA1 as the potential modulating factor to glycolysis. Besides, the expression of genes encoding glycolytic enzymes positively correlated with genes in cell cycle.Interpretation: This is the first study to identify gene expression signatures that reflect glycolysis activity, which can be easily applied to large numbers of patient samples. Our analysis establishes a computational framework for characterizing glycolysis activity using gene expression data and defines correlation of glycolysis with the hypoxia microenvironment, tumor cell cycle and proliferation at a pan-cancer landscape. The findings suggest that the mechanisms whereby hypoxia influence glycolysis are likely multifactorial.Our finding is significant not just in demonstrating definition value for glycolysis but also in providing a comprehensive molecular-level understanding of glycolysis and suggesting a framewo...

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Lactic Acid: No Longer an Inert and End-Product of Glycolysis

Cited by 212 publications

References 156 publications

Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism

Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism

Sprayable and biodegradable, intrinsically adhesive wound dressing with antimicrobial properties

Persistent cell proliferation signals correlates with increased glycolysis in tumor hypoxia microenvironment across cancer types

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