Exercise metabolism and adaptation in skeletal muscle

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 24(9), С. 607 - 632

Опубликована: Май 24, 2023

Язык: Английский

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Post‐translational modifications of histones: Mechanisms, biological functions, and therapeutic targets

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 20, 2023

Abstract Histones are DNA‐binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute “histone code.” The relationship between their combination biological function can be used an important epigenetic marker. Methylation demethylation of same residue, acetylation deacetylation, phosphorylation dephosphorylation, even methylation different residues cooperate or antagonize with each other, forming a complex network. Histone‐modifying enzymes, cause numerous codes, have become hot topic research on cancer therapeutic targets. Therefore, thorough understanding role post‐translational modifications (PTMs) cell life activities is very for preventing treating human diseases. In this review, several most thoroughly studied newly discovered PTMs introduced. Furthermore, we focus histone‐modifying enzymes carcinogenic potential, abnormal modification sites tumors, multiple essential molecular regulation mechanism. Finally, summarize missing areas current point out direction future research. We hope to provide comprehensive promote further field.

Язык: Английский

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Lactate as a myokine and exerkine: drivers and signals of physiology and metabolism

Journal of Applied Physiology, Год журнала: 2023, Номер 134(3), С. 529 - 548

Опубликована: Янв. 12, 2023

No longer viewed as a metabolic waste product and cause of muscle fatigue, contemporary view incorporates the roles lactate in metabolism, sensing signaling normal well pathophysiological conditions. Lactate exists millimolar concentrations muscle, blood, other tissues can rise more than an order magnitude result increased production clearance limitations. exerts its powerful driver-like influence by mass action, redox change, allosteric binding, mechanisms described this article. Depending on condition, such during rest exercise, following carbohydrate nutrition, injury, or pathology, serve myokine exerkine with autocrine-, paracrine-, endocrine-like functions that have important basic translational implications. For instance, is: involved reproductive biology, fueling heart, adaptation, brain executive function, growth development, treatment for inflammatory also works many factors controlling cardiac output pulmonary ventilation exercise. Ironically, be disruptive processes insulin secretion when insertion transporters into pancreatic β-cell membranes is not suppressed, carcinogenesis suppress are inhibited, whereas promote upregulated. areas intermediary mitochondrial biogenesis, neurobiology, gut physiology, appetite regulation, overall health vigor. The various reviewed.NEW & NOTEWORTHY relatively new rapidly changing field. As physiological signal both independently concert signals. operates via covalent binding canonical signaling, lactylation DNA. element feedback loops cardiopulmonary regulation. From conception through aging only exerkine, but it certainly deserves consideration signal.

Язык: Английский

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Histone lactylation couples cellular metabolism with developmental gene regulatory networks

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 2, 2024

Abstract Embryonic cells exhibit diverse metabolic states. Recent studies have demonstrated that reprogramming drives changes in cell identity by affecting gene expression. However, the connection between cellular metabolism and expression remains poorly understood. Here we report glycolysis-regulated histone lactylation couples state of embryonic with chromatin organization regulatory network (GRN) activation. We found marks genomic regions glycolytic tissues, like neural crest (NC) pre-somitic mesoderm. Histone occurs loci NC genes as these upregulate glycolysis. This process promotes accessibility active enhancers deployment GRN. Reducing deposition mark targeting LDHA/B leads to downregulation impairment migration. The lactyl-CoA on histones at is supported a mechanism involves transcription factors SOX9 YAP/TEAD. These findings define an epigenetic integrates GRNs orchestrate development.

Язык: Английский

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Adipose tissue retains an epigenetic memory of obesity after weight loss

Nature, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 18, 2024

Abstract Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity 1,2 . However, maintaining loss considerable challenge, especially as the seems retain an obesogenic memory that defends against changes 3,4 Overcoming this barrier for long-term treatment success difficult because molecular mechanisms underpinning phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show both human mouse adipose tissues cellular transcriptional after appreciable loss. Furthermore, find persistent obesity-induced alterations epigenome of adipocytes negatively affect their function response stimuli. Mice carrying accelerated rebound gain, epigenetic can explain future deregulation further high-fat diet feeding. In summary, our findings indicate existence memory, on basis stable changes, probably other cell types. These seem prime cells pathological responses environment, contributing problematic ‘yo-yo’ effect often seen with dieting. Targeting these could management outcomes.

Язык: Английский

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Ubiquitous protein lactylation in health and diseases

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Фев. 5, 2024

Abstract For decades, lactate has been considered a byproduct of glycolysis. The shuttle hypothesis shifted the paradigm, demonstrating that not only plays important roles in cellular metabolism but also communications, which can transcend compartment barriers and occur within among different cells, tissues organs. Recently, discovery induce novel post-translational modification, named lysine lactylation (Kla), brings forth new avenue to study nonmetabolic functions for lactate, inspired ‘gold rush’ academic commercial interest. Zhang et al. first showed Kla is manifested histones as epigenetic marks, then mounting evidences demonstrated occurs diverse non-histone proteins. widespread faithfully orchestrates numerous biological processes, such transcription, inflammatory responses. Notably, dysregulation touches myriad pathological processes. In this review, we comprehensively reviewed curated existing literature retrieve identified sites on both proteins summarized recent major advances toward its regulatory mechanism. We thoroughly investigated function underlying signaling pathway summarize how regulates various processes normal physiological states. addition, further highlight effects development human diseases including inflammation response, tumorigenesis, cardiovascular nervous system other complex diseases, might potentially contribute deeply understanding interpreting mechanism pathogenicity. Graphical

Язык: Английский

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Lactylation: the novel histone modification influence on gene expression, protein function, and disease

Clinical Epigenetics, Год журнала: 2024, Номер 16(1)

Опубликована: Май 29, 2024

Abstract Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone resurgence in scientific interest since the discovery of Warburg effect tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair function immune cells within microenvironments. Nevertheless, precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, been found to induce posttranslational modification, lactylation, may offer insight into acid's non-metabolic functions. Notably, modification proteins by lactylation emerged crucial mechanism which lactate regulates cellular processes. This article provides an overview acidification, outlines potential “writers” “erasers” responsible for protein presents patterns across different organisms, discusses diverse physiological roles lactylation. Besides, highlights latest research progress concerning regulatory pathological processes underscores its significance future investigations.

Язык: Английский

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Histone lactylation: from tumor lactate metabolism to epigenetic regulation

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(5), С. 1833 - 1854

Опубликована: Янв. 1, 2024

The Warburg Effect is one of the most well-known cancer hallmarks.This metabolic pattern centered on lactate has extremely complex effects various aspects tumor microenvironment, including remodeling, immune suppression, cell migration, and drug resistance development.Based accumulating evidence, metabolites are likely to participate in regulation biological processes microenvironment form a feedback loop.Therefore, further revealing key mechanism lactate-mediated oncological reasonable scientific idea.The discovery refinement histone lactylation recent years laid firm foundation for above idea.Histone post-translational modification that occurs at lysine sites histones.Specific enzymes, known as "writers" "erasers", catalyze addition or removal, respectively, lactacyl group target sites.An increasing number investigations have reported this multiple cellular procedures.In review, we discuss close connection between series tumorigenesis, infiltration, energy metabolism.Finally, review provides insightful perspectives, identifying promising avenues exploration potential clinical application field research.

Язык: Английский

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Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation

Circulation Research, Год журнала: 2024, Номер 134(11), С. 1427 - 1447

Опубликована: Апрель 17, 2024

Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and commonly observed in patients with kidney disease, diabetes, aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, key regulator apo (apolipoprotein) A-IV-induced progression; however, its role poorly understood.

Язык: Английский

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Augmentation of scleral glycolysis promotes myopia through histone lactylation

Cell Metabolism, Год журнала: 2024, Номер 36(3), С. 511 - 525.e7

Опубликована: Янв. 16, 2024

Язык: Английский

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