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References from The role of lysine acylation in metabolic dysregulation and inflammatory responses within the hepatic immune microenvironment of MASLD. Local targets link to admitted publications; unresolved targets remain external evidence.
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Histone lactylation in macrophage biology and disease: from plasticity regulation to therapeutic implications
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Mitochondrial pyruvate carrier 1 regulates fatty acid synthase lactylation and mediates treatment of nonalcoholic fatty liver disease
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A critical role for the mitochondrial pyruvate carrier in hepatic stellate cell activation
10.1016/j.jcmgh.2025.101517 · 2025 · External reference
Malonylation of acetyl-CoA carboxylase 1 promotes hepatic steatosis and is attenuated by ketogenic diet in NAFLD
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Crotonylation modification and its role in diseases
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Acetyl-CoA carboxylase inhibition reverses NAFLD and hepatic insulin resistance but promotes hypertriglyceridemia in rodents
10.1002/hep.30097 · 2018 · External reference
The regulatory enzymes and protein substrates for the lysine β-hydroxybutyrylation pathway
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Chemical biology approaches for investigating the functions of lysine acetyltransferases
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Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation
10.1016/j.molcel.2015.02.029 · 2015 · External reference
Post-translational lysine Ac(et)ylation in bacteria: a biochemical, structural, and synthetic biological perspective
10.3389/fmicb.2021.757179 · 2021 · External reference
Chemical and biochemical perspectives of protein lysine methylation
10.1021/acs.chemrev.8b00008 · 2018 · External reference
ATP-citrate lyase links cellular metabolism to histone acetylation
10.1126/science.1164097 · 2009 · External reference
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10.1074/jbc.m113.486753 · 2013 · External reference
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10.3389/fmolb.2024.1407505 · 2024 · External reference
Protein succinylation: regulating metabolism and beyond
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Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation
10.1016/j.celrep.2013.07.024 · 2013 · External reference
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Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase
10.1126/science.1207861 · 2011 · External reference
Metabolic regulation of gene expression by histone lactylation
10.1038/s41586-019-1678-1 · 2019 · External reference
SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
10.1038/nature08778 · 2010 · External reference
NAD+ in aging, metabolism, and neurodegeneration
10.1126/science.aac4854 · 2015 · External reference
The role of lactate and lactylation in the dysregulation of immune responses in psoriasis
10.1007/s12016-025-09037-2 · 2025 · External reference
Myeloid mas drives pyruvate kinase M2-mediated Spi1 lactylation to fuel inflammatory senescence in MASLD
10.1038/s41392-026-02704-6 · 2026 · External reference
Liver-spleen axis: deciphering a crucial crosstalk in non-alcoholic fatty liver disease progression and therapeutic implications
10.3748/wjg.119467 · 2026 · External reference
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10.3390/immuno4040030 · 2024 · External reference
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Social stress mobilizes hematopoietic stem cells to establish persistent splenic myelopoiesis
10.1016/j.celrep.2018.10.102 · 2018 · External reference
Bioactive lipid species and metabolic pathways in progression and resolution of nonalcoholic steatohepatitis
10.1053/j.gastro.2018.06.031 · 2018 · External reference
What are the common downstream molecular events between alcoholic and nonalcoholic fatty liver
10.1186/s12944-024-02031-1 · 2024 · External reference
Hepatocyte senescence predicts progression in non-alcohol-related fatty liver disease
10.1016/j.jhep.2012.10.031 · 2013 · External reference
The role of senescence in the development of nonalcoholic fatty liver disease and progression to nonalcoholic steatohepatitis
10.1002/hep.30834 · 2020 · External reference
The potential role of cellular senescence in non-alcoholic fatty liver disease
10.3390/ijms23020652 · 2022 · External reference
Cellular senescence drives age-dependent hepatic steatosis
10.1038/ncomms15691 · 2017 · External reference
Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function
10.1073/pnas.1519858113 · 2016 · External reference
Post-translational modulation of cell signalling through protein succinylation
10.37349/etat.2023.00196 · 2023 · External reference
Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development
10.3389/fimmu.2025.1531246 · 2025 · External reference
Up-regulated succinylation modifications induce a senescence phenotype in microglia by altering mitochondrial energy metabolism
10.1186/s12974-024-03284-4 · 2024 · External reference
Paracrine cellular senescence exacerbates biliary injury and impairs regeneration
10.1038/s41467-018-03299-5 · 2018 · External reference
Substance P increases liver fibrosis by differential changes in senescence of cholangiocytes and hepatic stellate cells
10.1002/hep.29138 · 2017 · External reference
Knockout of secretin receptor reduces biliary damage and liver fibrosis in Mdr2-/- mice by diminishing senescence of cholangiocytes
10.1038/s41374-018-0093-9 · 2018 · External reference
Lung myofibroblasts promote macrophage profibrotic activity through lactate-induced histone lactylation
10.1165/rcmb.2020-0360oc · 2021 · External reference
Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions
10.15252/embj.201591271 · 2015 · External reference
SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome
10.1016/j.molcel.2011.07.019 · 2011 · External reference
SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine
10.1038/nature12038 · 2013 · External reference
hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase
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10.1038/s41423-020-00558-8 · 2021 · External reference
Hepatic macrophages in liver injury
10.3389/fimmu.2020.00322 · 2020 · External reference
Histone lactylation: a new role for glucose metabolism
10.1016/j.tibs.2019.12.004 · 2020 · External reference
Lactylation: a passing fad or the future of posttranslational modification
10.1007/s10753-022-01637-w · 2022 · External reference
Crosstalk between glucose metabolism, lactate production and immune response modulation
10.1016/j.cytogfr.2022.11.001 · 2022 · External reference
Lysine catabolism reprograms tumour immunity through histone crotonylation
10.1038/s41586-023-06061-0 · 2023 · External reference
Lactylation: the novel histone modification influence on gene expression, protein function, and disease
10.1186/s13148-024-01682-2 · 2024 · External reference
Histone lactylation: from tumor lactate metabolism to epigenetic regulation
10.7150/ijbs.91492 · 2024 · External reference
The m6A reader IGF2BP2 regulates glycolytic metabolism and mediates histone lactylation to enhance hepatic stellate cell activation and liver fibrosis
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Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics
10.1186/s43556-026-00490-9 · 2026 · External reference
Lactate transporter MCT1 in hepatic stellate cells promotes fibrotic collagen expression in nonalcoholic steatohepatitis
10.7554/elife.89136 · 2024 · External reference
Lactate transporter MCT4 regulates the hub genes for lipid metabolism and inflammation to attenuate intracellular lipid accumulation in non-alcoholic fatty liver disease
10.1016/j.gendis.2025.101554 · 2025 · External reference
Loss of LCAT function aggravates metabolic-associated steatohepatitis (MASH) in golden Syrian hamster
10.1042/cs20257764 · 2025 · External reference
The m6A methyltransferase Mettl3 deficiency attenuates hepatic stellate cell activation and liver fibrosis
10.1016/j.ymthe.2022.07.020 · 2022 · External reference
The IGF2BP3/notch/Jag1 pathway: a key regulator of hepatic stellate cell ferroptosis in liver fibrosis
10.1002/ctm2.1793 · 2024 · External reference
RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy
10.1038/s41392-024-01777-5 · 2024 · External reference
Crosstalk between lactylation and RNA modifications in tumorigenesis: mechanisms and therapeutic implications
10.1186/s40364-025-00824-9 · 2025 · External reference
Decoding m6A RNA methylation in kidney disorders: from molecular insights to therapeutic strategies
10.1186/s12967-025-06817-4 · 2025 · External reference
Regulation of hepatic stellate cell phenotypes in metabolic dysfunction–associated steatohepatitis
10.1053/j.gastro.2025.03.010 · 2025 · External reference
The role of liver sinusoidal endothelial cells in liver diseases: key players in health and pathology
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The transcription factor KLF2 mediates hepatic endothelial protection and paracrine endothelial–stellate cell deactivation induced by statins
10.1016/j.jhep.2012.08.026 · 2013 · External reference
Aging aggravates liver fibrosis through downregulated hepatocyte SIRT1-induced liver sinusoidal endothelial cell dysfunction
10.1097/hc9.0000000000000350 · 2024 · External reference
Liver sinusoidal endothelial cells in hepatic fibrosis
10.1002/hep.27376 · 2015 · External reference
Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3
10.1161/atvbaha.114.304277 · 2015 · External reference
SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase
10.1073/pnas.0704329104 · 2007 · External reference
Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating sirtuin 1 expression
10.1016/j.jhep.2016.11.004 · 2017 · External reference
Sirtuin 1 ameliorates defenestration in hepatic sinusoidal endothelial cells during liver fibrosis via inhibiting stress-induced premature senescence
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Resveratrol improves intrahepatic endothelial dysfunction and reduces hepatic fibrosis and portal pressure in cirrhotic rats
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KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins
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Suppression of PFKFB3-driven glycolysis restrains endothelial-to-mesenchymal transition and fibrotic response
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MOF as an evolutionarily conserved histone crotonyltransferase and transcriptional activation by histone acetyltransferase-deficient and crotonyltransferase-competent CBP/p300
10.1038/celldisc.2017.16 · 2017 · External reference
SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks
10.1016/j.cmet.2013.11.013 · 2013 · External reference
The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5)*
10.1074/jbc.m112.384511 · 2012 · External reference
SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways
10.1016/j.molcel.2013.06.001 · 2013 · External reference
SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target
10.1016/j.molcel.2015.05.022 · 2015 · External reference
Lysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain
10.1074/jbc.m117.785022 · 2017 · External reference
The mitochondrial acylome emerges: proteomics, regulation by sirtuins, and metabolic and disease implications
10.1016/j.cmet.2018.01.016 · 2018 · External reference
Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity
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SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells
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Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation
10.2337/db12-1650 · 2013 · External reference
Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex
10.1016/j.molcel.2013.12.026 · 2014 · External reference
SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
10.1016/j.cell.2009.02.026 · 2009 · External reference
Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation
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Distinct contributions of metabolic dysfunction and genetic risk factors in the pathogenesis of non-alcoholic fatty liver disease
10.1016/j.jhep.2021.10.013 · 2022 · External reference
Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase
10.1038/sj.emboj.7600244 · 2004 · External reference
Stat3 dimerization regulated by reversible acetylation of a single lysine residue
10.1126/science.1105166 · 2005 · External reference
An acetylation switch of the NLRP3 inflammasome regulates aging-associated chronic inflammation and insulin resistance
10.1016/j.cmet.2020.01.009 · 2020 · External reference
Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging
10.1016/j.cmet.2013.09.010 · 2013 · External reference
The role of NLRP3 inflammasome in aging and age-related diseases
10.1186/s12979-023-00395-z · 2024 · External reference
SIRT5 safeguards against T-2 toxin induced liver injury by repressing iron accumulation, oxidative stress, and the activation of NLRP3 inflammasome
10.1016/j.taap.2024.117084 · 2024 · External reference
Unresolved reference
External reference
Smad3 is acetylated by p300/CBP to regulate its transactivation activity
10.1038/sj.onc.1209826 · 2007 · External reference
Acetylation of Smad2 by the Co-activator p300 regulates activin and transforming growth factor β response *
10.1074/jbc.m700085200 · 2007 · External reference
The DNA binding activities of Smad2 and Smad3 are regulated by coactivator-mediated acetylation *
10.1074/jbc.m607868200 · 2006 · External reference
Brd4 activates P-TEFb for RNA polymerase II CTD phosphorylation
10.1093/nar/gku449 · 2014 · External reference
Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4
10.1016/j.molcel.2005.06.029 · 2005 · External reference
Two-pronged binding with bromodomain-containing protein 4 liberates positive transcription elongation factor b from inactive ribonucleoprotein complexes *
10.1074/jbc.m111.282855 · 2012 · External reference
Legumain promotes tubular ferroptosis by facilitating chaperone-mediated autophagy of GPX4 in AKI
10.1038/s41419-020-03362-4 · 2021 · External reference
Chaperone-mediated autophagy is involved in the execution of ferroptosis
10.1073/pnas.1819728116 · 2019 · External reference
GPX4 degradation via chaperone-mediated autophagy contributes to antimony-triggered neuronal ferroptosis
10.1016/j.ecoenv.2022.113413 · 2022 · External reference
GPX4 degradation contributes to heat stress-induced liver injury via chaperone-mediated autophagy
10.1016/j.bbamcr.2025.119988 · 2025 · External reference
HAT1/HDAC2 mediated ACSL4 acetylation confers radiosensitivity by inducing ferroptosis in nasopharyngeal carcinoma
10.1038/s41419-025-07477-4 · 2025 · External reference
Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation
10.1038/s41420-025-02859-1 · 2026 · External reference
SIRT4-mediated deacetylation of PRDX3 attenuates liver ischemia reperfusion injury by suppressing ferroptosis
10.7150/ijbs.114510 · 2025 · External reference
Metabolic regulation of pyroptotic cell death expands the therapeutic landscape for treating inflammatory disease
10.1038/s41392-021-00467-w · 2021 · External reference
Modes of p53 regulation
10.1016/j.cell.2009.04.050 · 2009 · External reference
GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis
10.1084/jem.20160061 · 2016 · External reference
Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated gq signaling
10.1016/j.celrep.2021.109246 · 2021 · External reference
Integrin β1-enriched extracellular vesicles mediate monocyte adhesion and promote liver inflammation in murine NASH
10.1016/j.jhep.2019.07.019 · 2019 · External reference
Lipid-induced signaling causes release of inflammatory extracellular vesicles from hepatocytes
10.1053/j.gastro.2015.12.037 · 2016 · External reference
Hepatocyte-derived extracellular vesicles promote endothelial inflammation and atherogenesis via microRNA-1
10.1016/j.jhep.2019.09.014 · 2020 · External reference
Hepatocyte-derived lipotoxic extracellular vesicle sphingosine 1-phosphate induces macrophage chemotaxis
10.3389/fimmu.2018.02980 · 2018 · External reference
Circulating extracellular vesicles with specific proteome and liver MicroRNAs are potential biomarkers for liver injury in experimental fatty liver disease
10.1371/journal.pone.0113651 · 2014 · External reference
Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis [S
10.1194/jlr.r066357 · 2016 · External reference
Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease
10.1016/j.cmet.2011.11.004 · 2011 · External reference
Targeting hepatic macrophages to treat liver diseases
10.1016/j.jhep.2017.02.026 · 2017 · External reference
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
10.1038/nature11986 · 2013 · External reference
Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system
10.1038/nrgastro.2017.183 · 2018 · External reference
NASH limits anti-tumour surveillance in immunotherapy-treated HCC
10.1038/s41586-021-03362-0 · 2021 · External reference
Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches
10.1016/j.cell.2021.12.018 · 2022 · External reference
Mechanisms of hepatic stellate cell activation
10.1038/nrgastro.2017.38 · 2017 · External reference
Mitochondrial pyruvate carrier function in health and disease across the lifespan
10.3390/biom10081162 · 2020 · External reference
Single-cell spatial proteomics maps human liver zonation patterns and their vulnerability to disruption in tissue architecture
10.1038/s42255-026-01459-2 · 2026 · External reference
Spatial single-cell mass spectrometry defines zonation of the hepatocyte proteome
10.1038/s41592-023-02007-6 · 2023 · External reference
Deep visual proteomics maps proteotoxicity in a genetic liver disease
10.1038/s41586-025-08885-4 · 2025 · External reference
Adenine base editing and prime editing of chemically derived hepatic progenitors rescue genetic liver disease
10.1016/j.stem.2021.04.010 · 2021 · External reference
Foundations of immunometabolism and implications for metabolic health and disease
10.1016/j.immuni.2017.08.009 · 2017 · External reference
Targeting lactylation: from metabolic reprogramming to precision therapeutics in liver diseases
10.3390/biom15081178 · 2025 · External reference
Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations
10.1016/j.cmet.2023.08.002 · 2023 · External reference
AGA clinical practice update on the role of noninvasive biomarkers in the evaluation and management of nonalcoholic fatty liver disease: expert review
10.1053/j.gastro.2023.06.013 · 2023 · External reference
Plasma extracellular vesicles contain protein biomarkers for capturing stages of metabolic dysfunction-associated steatotic liver disease: a preliminary exploratory study
10.3390/biom15111596 · 2025 · External reference
Characterization and proteome of circulating extracellular vesicles as potential biomarkers for NASH
10.1002/hep4.1556 · 2020 · External reference
Non-invasive diagnosis and monitoring of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis
10.1016/s2468-1253(23)00066-3 · 2023 · External reference
Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours
10.1038/nature24028 · 2017 · External reference
Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing
10.1021/ja505986a · 2014 · External reference
Resolving the fibrotic niche of human liver cirrhosis at single-cell level
10.1038/s41586-019-1631-3 · 2019 · External reference
Single-cell technologies in hepatology: new insights into liver biology and disease pathogenesis
10.1038/s41575-020-0304-x · 2020 · External reference
Metabolic regulation of gene expression by histone lysine β-hydroxybutyrylation
10.1016/j.molcel.2016.03.036 · 2016 · External reference
Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis
10.1126/scitranslmed.aba4448 · 2020 · External reference
From NASH to HCC: current concepts and future challenges
10.1038/s41575-019-0145-7 · 2019 · External reference
