Lactylation in health and disease: physiological or pathological?

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1787 - 1821

Published: Jan. 2, 2025

Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles different aspects of energy metabolism signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as novel posttranslational modification (PTM). Research indicates that Kla essential balancing mechanism variety organisms involved many biological processes pathways. closely related to disease development represents potential important new drug target. In line with existing reports, we searched for newly discovered sites on histone nonhistone proteins; reviewed the mechanisms (particularly focusing enzymes directly reversible regulation Kla, including "writers" (modifying enzymes), "readers" (modification-binding "erasers" (demodifying enzymes); summarized crosstalk between PTMs help researchers better understand widespread distribution diverse functions. Furthermore, considering "double-edged sword" role both pathological contexts, this review highlights "beneficial" states (energy metabolism, inflammatory responses, cell fate determination, development, etc.) "detrimental" pathogenic or inducive effects processes, particularly malignant tumors complex nontumor diseases. We also clarify molecular health disease, discuss feasibility therapeutic Finally, describe detection technologies their applications diagnosis clinical settings, aiming provide insights treatment diseases accelerate translation from laboratory research practice.

Language: Английский

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Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 9, 2025

The gut microbiota plays a pivotal role in anxiety regulation through pathways involving neurotransmitter production, immune signaling, and metabolic interactions. Among these, gut-derived serotonin (5-hydroxytryptamine, 5-HT), synthesized from tryptophan metabolism, has been identified as key mediator. However, it remains unclear whether specific microbial factors regulate metabolism to influence 5-HT production regulation. In this study, we analyzed 110 athletes undergoing closed training found that fecal lactate levels were significantly associated with indicators. We observed significant negative correlation between Akkermansia abundance athletes. Co-supplementation muciniphila (A. muciniphila) modulated by increasing enzyme TPH1 reducing IDO1, thus shifting kynurenine (Kyn) 5-HT. addition, enhanced the propionate capacity of A. muciniphila, potentially contributing reduction mice. Taken together, these findings suggest enteric collaboratively restore imbalance leading increased activity alleviating phenotypes. This study highlights intricate interplay metabolites regulation, offering potential avenues for microbiota-targeted therapeutic strategies anxiety.

Language: Английский

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Neurological mechanism-based analysis of the role and characteristics of physical activity in the improvement of depressive symptoms

Reviews in the Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Depression is a common mental disorder characterized by high prevalence and significant adverse effects, making the searching for effective interventions an urgent priority. In recent years, physical activity (PA) has increasingly been recognized as standard adjunctive treatment disorders owing to its low cost, easy application, efficiency. Epidemiological data shows positive preventive therapeutic effects of PA on illnesses such depression. This article systematically describes prophylactic depression biological basis. A comprehensive literature analysis reveals that significantly improves depressive symptoms upregulating expression “exerkines” irisin, adiponectin, BDNF positively impacting neuropsychiatric conditions. particular, lactate could also play critical role in ameliorating due findings about protein lactylation novel post-transcriptional modification. The suggests terms brain structure, may improve hippocampal volume, basal ganglia (neostriatum, caudate-crustal nucleus) PFC density patients with MDD. summary, this study elucidates multifaceted potential mechanisms particular emphasis roles various exerkines. Future research further investigate different types, intensities, durations depression, well how better integrate into existing strategies achieve optimal outcomes health interventions.

Language: Английский

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Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 22, 2025

Physical exercise effectively prevents anxiety disorders caused by environmental stress. The neural circuitry mechanism, however, remains incomplete. Here, we identified a previously unrecognized pathway originating from the primary motor cortex (M1) to medial prefrontal (mPFC) via ventromedial thalamic (VM) nuclei in male mice. Besides anatomical evidence, both ex vivo and recordings showed enhanced excitability of M1-VM inputs prelimbic (PrL) region mPFC upon 14-day treadmill on chronic restraint stress (CRS) mouse model. Further functional interrogations demonstrated that activation this circuit is necessary sufficient direct anxiolytic effect training CRS Our findings provide more insights into circuits connecting mental regions under paradigm implicate potential targets for neuromodulation treating disorders. relieves disorders, while authors show input cortex, nuclei.

Language: Английский

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Non-histone lactylation: unveiling its functional significance

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 24, 2025

Lactylation, a newly discovered protein posttranslational modification (PTM) in 2019, primarily occurs on lysine residues. Lactylation of histones was initially identified, and subsequent studies have increasingly demonstrated its widespread presence non-histone proteins. Recently, high-throughput proteomics identified large number lactylated proteins sites, revealing their global regulatory role disease development. Notably, this is catalyzed by lactyltransferase reversed delactylase, with numerous new enzymes, such as AARS1/2, reported to be involved. Specifically, these revealed how lactylation exerts influence through alterations spatial conformation, molecular interactions, enzyme activity subcellular localization. Indeed, implicated various physiological pathological processes, including tumor development, cardiovascular cerebrovascular diseases, immune cell activation psychiatric disorders. This review provides the latest advancements research roles lactylation, highlighting crucial scientific importance for future studies.

Language: Английский

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Lactate and Lactylation: Dual Regulators of T-Cell-Mediated Tumor Immunity and Immunotherapy

Biomolecules, Journal Year: 2024, Volume and Issue: 14(12), P. 1646 - 1646

Published: Dec. 21, 2024

Lactate and its derivative, lactylation, play pivotal roles in modulating immune responses within the tumor microenvironment (TME), particularly T-cell-mediated cancer immunotherapy. Elevated lactate levels, a hallmark of Warburg effect, contribute to suppression through CD8+ T cell functionality by promoting regulatory (Treg) activity. Lactylation, post-translational modification (PTM), alters histone non-histone proteins, influencing gene expression further reinforcing suppression. In complex TME, are not only associated with but can also, under certain conditions, exert immunostimulatory effects that enhance cytotoxic responses. This review describes dual lactylation immunity, analyzing how these factors evasion, therapeutic resistance, activation. Furthermore, article highlights emerging strategies aimed at inhibiting production or disrupting pathways achieve balanced regulation effects. These offer new insights into overcoming tumor-induced hold potential improve efficacy immunotherapies.

Language: Английский

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Functional mechanisms and potential therapeutic strategies for lactylation in liver disease

Life Sciences, Journal Year: 2025, Volume and Issue: 363, P. 123395 - 123395

Published: Jan. 13, 2025

Language: Английский

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The association between weekend warrior physical activity pattern and anxiety: evidence from a U.S. population-based study

BMC Psychiatry, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 25, 2025

This study investigates the association between Weekend Warrior (WW) pattern and risk of anxiety among American adults, offering insights into a more flexible exercise strategy for individuals with limited time regular during weekdays. We analyzed data from 2007–2012 National Health Nutrition Examination Survey (NHANES) to examine relationship different physical activity (PA) patterns anxiety. Multivariate logistic regression, subgroup interaction, restricted cubic spline analysis (RCS), sensitivity analyses were conducted assess this association. Compared inactive individuals, those engaging in WW (OR = 0.65, 95% CI: 0.48–0.90, p 0.010), insufficiently active 0.71, 0.62–0.82, < 0.001), or regularly 0.75, 0.65–0.87, 0.001) showed significantly lower Subgroup interaction revealed significant effect modification poverty income ratio (PIR) diabetes subgroups (P 0.05), while no interactions observed other variables. RCS nonlinear recreational moderate vigorous intensity 0.001). Sensitivity further confirmed stability findings. The was associated For unable consistently throughout week, offers practical alternative reducing anxiety, particularly levels diabetes.

Language: Английский

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Single-nucleus RNA sequencing uncovers metabolic dysregulation in the prefrontal cortex of major depressive disorder patients

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 3, 2025

Major depressive disorder (MDD) is a widespread psychiatric condition, recognized as the third leading cause of global disease burden in 2008. In context MDD, alterations synaptic transmission within prefrontal cortex (PFC) are associated with PFC hypoactivation, key factor cognitive function and mood regulation. Given high energy demands central nervous system, these changes suggest metabolic imbalance MDD patients. However, cellular mechanisms underlying this dysregulation remain not fully elucidated. This study employs single-nucleus RNA sequencing (snRNA-seq) data to predict dorsolateral (DLPFC) Our analysis revealed cell type-specific patterns, notably disruption oxidative phosphorylation carbohydrate metabolism DLPFC Gene set enrichment based on human phenotype ontology predicted serum lactate levels patients, corroborated by observed decrease patients compared 47 age-matched healthy controls (HCs). transcriptional offers novel insights into disturbances dynamics hypoactivation. These findings instrumental for comprehending pathophysiology may guide development innovative therapeutic strategies.

Language: Английский

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Is physical exercise associated with reduced adolescent social anxiety mediated by psychological resilience?: evidence from a longitudinal multi-wave study in China

Child and Adolescent Psychiatry and Mental Health, Journal Year: 2025, Volume and Issue: 19(1)

Published: March 5, 2025

The study aims to investigate whether physical exercise is associated with psychological resilience, thereby significantly affecting adolescent social anxiety, and analyze the longitudinal cross-temporal stability between these three interrelated factors. methodology involved a survey utilizing International Physical Activity Questionnaire (IPAQ), Connor-Davidson Resilience Scale (CD-RISC), Social Anxiety (SAS) across various regions in China, including Sichuan, Guangdong, Shanxi Province, Beijing. A total of 1259 participants were recruited from primary, middle, high schools, an average age 13.7 years. sample comprised 626 males 633 females. tracking approach was implemented, commencing June 2023, follow-up rounds scheduled every months, culminating four rounds. results are as follows: (1) positively correlated resilience (r = 0.35, p < 0.001) negatively anxiety - 0.26, 0.001); (2) could predict next period (PET1 → SAT2: β 0.31, (3) Psychological played mediating role association on PRT2: 0.42, PRT2 SAT3: 0.38, p-values 0.001). exercise, exhibit stability, has significant lagged effect anxiety. may indirectly reduce through its enhanced adolescents.

Language: Английский

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