{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:22:09Z","timestamp":1783012929808,"version":"3.54.6"},"reference-count":60,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008397","name":"Velux Fonden","doi-asserted-by":"publisher","award":["VELUX34148"],"award-info":[{"award-number":["VELUX34148"]}],"id":[{"id":"10.13039\/100008397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R105\u2010A9308"],"award-info":[{"award-number":["R105\u2010A9308"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R180\u20102014\u20102740"],"award-info":[{"award-number":["R180\u20102014\u20102740"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF20OC0065548"],"award-info":[{"award-number":["NNF20OC0065548"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Ketone bodies are liver\u2010derived circulating energy metabolites that positively impact most hallmarks of ageing. Ketone bodies increase during calorie restriction and fasting, two of the more widely perceived methods to increase health span. Adhering to a strict diet to increase ketogenesis is demanding, which leaves a significant unmet need for a pharmacological alternative. The present study hypothesised that chemical genetic screening can reveal novel proteins that will regulate ketogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      We developed phenotypic screening assays to determine ketone bodies in hepatocytes. We applied two libraries of annotated small molecule compounds to determine proteins regulating ketogenesis. Adenosine 3\u2032,5\u2032 cyclic monophosphate (cAMP) measurements, quantitative reverse transcription polymerase chain reaction (RT\u2010qPCR), western blotting and small interfering RNA (siRNA) silencing were performed to validate targets in hepatocytes. RT\u2010qPCR and proteomics were performed to validate targets in liver tissues.\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Drosophila melanogaster<\/jats:italic>\n                      <\/jats:styled-content>\n                      was used in a longevity assay. Mice were used to demonstrate regulation of ketogenesis in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Ketogenesis links pathways involved in metabolic health and longevity, identifying coactivator\u2010associated arginine methyltransferase 1 (CARM1) as a novel regulator. Joint pharmacological targeting of CARM1 and salt inducible kinases (SIK) synergise, resulting in high ketogenic induction in hepatocytes. Finally, we demonstrate the dual activation of ketogenesis with homeostatic blood\u2010glucose in non\u2010fasting mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Ketogenesis represents a promising biomarker and therapeutic target for metabolic interventions targeting age\u2010related diseases. Our data suggest that CARM1 and SIKs warrant further investigation for pharmacological induction of ketogenesis, with potential clinical applications in ageing\u2010associated metabolic dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70447","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:45:51Z","timestamp":1777509951000},"page":"4399-4415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual pharmacological targeting of coactivator\u2010associated arginine methyltransferase 1 (CARM1) and salt inducible kinase (SIK) drives ketogenesis in both hepatocytes and mice"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9100-6974","authenticated-orcid":false,"given":"T\u00e1bata","family":"Bergonci","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine Aarhus University  Aarhus 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