International Diabetes Federation. IDF Diabetes Atlas, 10th edn. Brussels, Belgium: 2021. https://www.diabetesatlas.org.

Wai-Sun Wong, V., Ekstedt, M., Lai-Hung Wong, G. & Hagström, H. Changing epidemiology, global trends and implications for outcomes of NAFLD. J. Hepatol. https://doi.org/10.1016/j.jhep.2023.04.036 (2023).

Afshin, A. et al. Health effects of overweight and obesity in 195 countries over 25 years. N. Engl. J. Med. 377, 13–27 (2017).

Article  PubMed  Google Scholar 

Malik, S. et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 110, 1245–1250 (2004).

Article  PubMed  Google Scholar 

Roth, G. A. et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study. J. Am. Coll. Cardiol. 76, 2982–3021 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Dagenais, G. R. et al. Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study. Lancet 395, 785–794 (2020).

Article  PubMed  Google Scholar 

National Health Expenditure Data: Historical. Center for Medicare & Medicaid Services. December 15, 2021. Accessed May 5, 2022. https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/NationalHealthAccountsHistorical.

Blom, N., Sicheritz-Pontén, T., Gupta, R., Gammeltoft, S. & Brunak, S. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 4, 1633–1649 (2004).

Article  CAS  PubMed  Google Scholar 

Levene, P. A. & Alsberg, C. L. The cleavage products of Vitellin. J. Biol. Chem. 2, 127–133 (1906).

Article  Google Scholar 

Burnett, G. & Kennedy, E. P. The enzymatic phosphorylation of proteins. J. Biol. Chem. 211, 969–980 (1954).

Article  CAS  PubMed  Google Scholar 

Allfrey, V. G., Faulkner, R. & Mirsky, A. E. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. Natl Acad. Sci. USA 51, 786–794 (1964).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Linn, T. C., Pettit, F. H. & Reed, L. J. Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc. Natl Acad. Sci. USA 62, 234–241 (1969).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tunyasuvunakool, K. et al. Highly accurate protein structure prediction for the human proteome. Nature 596, 590–596 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ramazi, S. & Zahiri, J. Posttranslational modifications in proteins: resources, tools and prediction methods. Database (Oxford) 2021, baab012. https://doi.org/10.1093/database/baab012 (2021).

Cohen, P., Cross, D. & Jänne, P. A. Kinase drug discovery 20 years after imatinib: progress and future directions. Nat. Rev. Drug Discov. 20, 551–569 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cohen, P. Protein kinases-the major drug targets of the twenty-first century? Nat. Rev. Drug Discov. 1, 309–315 (2002).

Article  CAS  PubMed  Google Scholar 

Liberale, L. et al. JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study. Eur. Heart J. https://doi.org/10.1093/eurheartj/ehac641 (2022).

Lally, J. S. V. et al. Inhibition of acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma. Cell Metab. 29, 174–182.e175 (2019).

Article  CAS  PubMed  Google Scholar 

Sacco, F. et al. Phosphoproteomics reveals the GSK3-PDX1 axis as a key pathogenic signaling node in diabetic islets. Cell Metab. 29, 1422–1432.e1423 (2019).

Article  CAS  PubMed  Google Scholar 

Zhang, D. et al. Metabolic regulation of gene expression by histone lactylation. Nature 574, 575–580 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin, J. & Pawson, T. Modular evolution of phosphorylation-based signalling systems. Philos. Trans. R. Soc. Lond. B Biol. Sci. 367, 2540–2555 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yin, C. et al. Phosphorylation-mediated assembly of a semisynthetic fluorescent protein for label-free detection of protein kinase activity. Anal. Chem. 87, 6311–6318 (2015).

Article  CAS  PubMed  Google Scholar 

Verdin, E. & Ott, M. 50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond. Nat. Rev. Mol. Cell Biol. 16, 258–264 (2015).

Article  CAS  PubMed  Google Scholar 

Davies, M. N. et al. The acetyl group buffering action of carnitine acetyltransferase offsets macronutrient-induced lysine acetylation of mitochondrial proteins. Cell Rep. 14, 243–254 (2016).

Article  CAS  PubMed  Google Scholar 

Christensen, D. G. et al. Mechanisms, detection, and relevance of protein acetylation in prokaryotes. mBio 10, e02708–18 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lei, L. et al. Histone deacetylase 3-selective inhibitor RGFP966 ameliorates impaired glucose tolerance through beta-cell protection. Toxicol. Appl. Pharm. 406, 115189 (2020).

Article  CAS  Google Scholar 

Kim, H. S. et al. Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metab. 12, 224–236 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lecce, L. et al. Histone deacetylase 9 promotes endothelial-mesenchymal transition and an unfavorable atherosclerotic plaque phenotype. J. Clin. Invest 131, e131178 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schoenheimer, R., Ratner, S. & Rittenberg, D. Studies in protein metabolism: VII. The metabolism of tyrosine. J. Biol. Chem. 127, 333–344 (1939).

Article  Google Scholar 

Husmann, D. & Gozani, O. Histone lysine methyltransferases in biology and disease. Nat. Struct. Mol. Biol. 26, 880–889 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang, Y. & Bedford, M. T. Protein arginine methyltransferases and cancer. Nat. Rev. Cancer 13, 37–50 (2013).

Article  CAS  PubMed  Google Scholar 

Carlson, S. M. & Gozani, O. Emerging technologies to map the protein methylome. J. Mol. Biol. 426, 3350–3362 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee, D. Y., Teyssier, C., Strahl, B. D. & Stallcup, M. R. Role of protein methylation in regulation of transcription. Endocr. Rev. 26, 147–170 (2005).

Article  CAS  PubMed  Google Scholar 

Wang, D. et al. Hepatocellular BChE as a therapeutic target to ameliorate hypercholesterolemia through PRMT5 selective degradation to restore LDL receptor transcription. Life Sci. 293, 120336 (2022).

Article  CAS  PubMed  Google Scholar 

Kim, H. et al. PRMT1 is required for the maintenance of mature beta-cell identity. Diabetes 69, 355–368 (2020).

Article  CAS  PubMed  Google Scholar 

Lin, L., Zhang, Q., Fan, H., Zhao, H. & Yang, Y. Myocardin-related transcription factor A mediates LPS-induced iNOS transactivation. Inflammation 43, 1351–1361 (2020).

Article  CAS  PubMed  Google Scholar 

Goldstein, G. et al. Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc. Natl Acad. Sci. USA 72, 11–15 (1975).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Callis, J. The ubiquitination machinery of the ubiquitin system. Arabidopsis Book 12, e0174 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Schulman, B. A. & Harper, J. W. Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nat. Rev. Mol. Cell Biol. 10, 319–331 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stewart, M. D., Ritterhoff, T., Klevit, R. E. & Brzovic, P. S. E2 enzymes: more than just middle men. Cell Res. 26, 423–440 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang, Q., Zhao, J., Chen, D. & Wang, Y. E3 ubiquitin ligases: styles, structures and functions. Mol. Biomed. 2, 23 (2021).

Article  PubMed