Enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 27, 2022

Abstract In mammals, nonrenewable primordial follicles are activated in an orderly manner to maintain the longevity of reproductive life. Mammalian target rapamycin (mTOR)-KIT ligand (KITL) signaling pre-granulosa cells and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-forkhead Box O3a (FOXO3a) oocytes important for follicle activation. The activation process is accompanied by enhancement energy metabolism, but causal relationship unclear. present study, levels glycolysis-related proteins GLUT4, HK1, PFKL, PKM2 were significantly increased granulosa decreased during mouse primordial-to-primary transition. Both short-term pyruvate deprivation vitro acute fasting vivo gene protein levels, AMPK activity, mTOR activity ovaries. downstream pathways Akt FOXO3a phosphorylated, resulting blockade glycolysis 2-deoxyglucose (2-DG), not communication network between oocyte KIT inhibitor ISCK03, deprivation-promoted activity. Glycolysis was also human transition, promoted increasing ovarian tissues. Taken together, enhanced promotes through signaling. These findings provide new insight into glycolytic disorders POI/PCOS.

Language: Английский

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Metabolic reprogramming and polarization of microglia in Parkinson’s disease: Role of inflammasome and iron

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 90, P. 102032 - 102032

Published: Aug. 10, 2023

Language: Английский

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Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 13, 2023

Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves switch from oxidative phosphorylation (OXPHOS) glycolysis or alterations other pathways. However, most experimental findings have been acquired murine cells, and little known about human microglia. In this study, we investigate transcriptomic, proteomic, profiles mouse iPSC-derived microglia challenged with TLR4 agonist LPS. We demonstrate that both species display shift an overall increased glycolytic gene signature LPS treatment. The characterized by upregulation hexokinases phosphofructokinases study provides direct comparison metabolism between microglia, highlighting species-specific pathways involved immunometabolism importance considering these differences translational research.

Language: Английский

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Inflammatory Fibroblast‐Like Synoviocyte‐Derived Exosomes Aggravate Osteoarthritis via Enhancing Macrophage Glycolysis

Advanced Science, Journal Year: 2024, Volume and Issue: 11(14)

Published: Feb. 11, 2024

Abstract The severity of osteoarthritis (OA) and cartilage degeneration is highly associated with synovial inflammation. Although recent investigations have revealed a dysregulated crosstalk between fibroblast‐like synoviocytes (FLSs) macrophages in the pathogenesis synovitis, limited knowledge available regarding involvement exosomes. Here, increased exosome secretion observed FLSs from OA patients. Notably, internalization inflammatory FLS‐derived exosomes (inf‐exo) can enhance M1 polarization macrophages, which further induces an OA‐like phenotype co‐cultured chondrocytes. Intra‐articular injection inf‐exo synovitis exacerbates progression murine models. In addition, it demonstrated that stimulation triggers activation glycolysis. Inhibition glycolysis using 2‐DG successfully attenuates excessive triggered by inf‐exo. Mechanistically, HIF1A identified as determinant transcription factor, inhibition which, both pharmacologically or genetically, relieves macrophage inflammation inf‐exo‐induced hyperglycolysis. Furthermore, vivo administration inhibitor alleviates experimental OA. results provide novel insights into pathogenesis, suggesting dysfunction represents attractive target for therapy.

Language: Английский

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Emerging role of senescent microglia in brain aging-related neurodegenerative diseases

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 20, 2024

Abstract Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain pathogenesis of these conditions remains inadequately understood. Cellular senescence considered to contribute cellular dysfunction inflammaging. According threshold theory senescent cell accumulation, vulnerability associated with rates generation clearance within brain. Given role microglia in eliminating cells, accumulation may lead acceleration aging, contributing inflammaging increased diseases. In this review, we propose idea that microglia, which notably vulnerable could potentially serve as central catalyst progression The are emerging promising target mitigating

Language: Английский

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Brain energy metabolism: A roadmap for future research

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: 168(5), P. 910 - 954

Published: Jan. 6, 2024

Although we have learned much about how the brain fuels its functions over last decades, there remains still to discover in an organ that is so complex. This article lays out major gaps our knowledge of interrelationships between metabolism and function, including biochemical, cellular, subcellular aspects functional imaging adult brain, as well during development, aging, disease. The focus on unknowns substrates associated transporters, roles insulin lipid droplets, emerging role microglia, mysteries cofactor signaling molecule NAD

Language: Английский

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TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysis

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 13, 2025

Traumatic brain injury (TBI) is characterized by high mortality and disability rates. Disease-associated microglia (DAM) are a newly discovered subtype of microglia. However, their presence function in the acute phase TBI remain unclear. Although glycolysis important for microglial differentiation, its regulatory role DAM transformation during still In this study, we investigated functions DAM-like cells mice, as well relationship between glycolysis. controlled cortical impact model was used to induce adult male wild-type (WT) C57BL/6 mice TREM2 knockout mice. Various techniques were assess effects on cells, including RT‒qPCR, immunofluorescence assays, behavioural tests, extracellular acidification rate (ECAR) Western blot analysis, cell magnetic sorting culture, glucose lactate flow cytometry. observed depended expression. impaired neurological recovery possibly due part clearing debris secreting VEGFa BDNF. Moreover, exhibited significantly increased glycolytic activity. regulated AKT‒mTOR‒HIF-1α pathway TBI. The increase partially contributed Taken together, results our study demonstrated that present might influence modulating Our provide new possible intervening

Language: Английский

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Enhanced glycolysis-derived lactate promotes microglial activation in Parkinson’s disease via histone lactylation

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 3, 2025

Language: Английский

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Metabolic reprogramming mediates hippocampal microglial M1 polarization in response to surgical trauma causing perioperative neurocognitive disorders

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: Nov. 13, 2021

Microglial polarization toward pro-inflammatory M1 phenotype are major contributors to the development of perioperative neurocognitive disorders (PNDs). Metabolic reprogramming plays an important role in regulating microglial polarization. We therefore hypothesized that surgical trauma can activate by metabolic induce hippocampal neuroinflammation and subsequent postoperative cognitive impairment.We used aged mice establish a model PNDs, investigated whether induced reprograming hippocampus using PET/CT GC/TOF-MS based metabolomic analysis. then determined effect glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on polarization, neuroinflammation, function at 3 d after surgery.We found surgery group had less context-related freezing time than either control or anesthesia (P < 0.05) without significant difference tone-related > 0.05). The level Iba-1 fluorescence intensity were significantly increased accompanied activated morphological changes microglia expression iNOS/CD86 (M1 marker) enriched from metabolomics analysis indicated provoked oxidative phosphorylation glycolysis hippocampus. Inhibition 2-DG alleviated increase (CD86+CD206-) up-regulation mediators (IL-1β IL-6) Furthermore, inhibition ameliorated dependent deficit caused trauma.Metabolic is crucial for PNDs. Manipulating metabolism might provide valuable therapeutic strategy treating

Language: Английский

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Parkinson's disease: connecting mitochondria to inflammasomes

Trends in Immunology, Journal Year: 2022, Volume and Issue: 43(11), P. 877 - 885

Published: Oct. 11, 2022

Language: Английский

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