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However, the molecular mechanisms underlying their beneficial effects remain incompletely understood. In this study, we assessed the metabolomic and lipidomic impact of CBD and CBG in a mouse model of diet\u2010induced obesity and MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Male C57Bl\/6 mice fed on a high\u2010fat diet for 14\u2009weeks were treated for 4\u2009weeks with daily intraperitoneal CBD, CBG or vehicle. Assessments included body composition, indirect calorimetry, glucose tolerance, serum biochemistry and VLDL\u2010triglyceride profiling. Hepatic mechanisms were examined by metabolomics, lipidomics, creatine kinase activity, cathepsin activity\u2010based probes and gene\/protein expression, with a choline\u2010deficient diet cohort to test phospholipid\u2010dependence of CBG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>CBD or CBG treatment improved glycaemic control, reduced hepatic triglycerides and normalised serum lipids, without affecting energy expenditure. Metabolomics revealed increased hepatic phosphocreatine and creatine with enhanced creatine kinase activity, indicating phosphocreatine\u2010based energy buffering independent of fatty acid oxidation changes. Lipidomics showed reduced triglycerides and ceramides, with increased phospholipids and lysobisphosphatidic acids, correlating with restored hepatic cathepsin activity and improved lysosomal lipid degradation. CBG was ineffective in choline\u2010deficient MASLD, indicating phospholipid pathway dependence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These findings identify a novel, endocannabinoid system\u2010independent mechanism by which CBD and CBG enhance hepatic energy buffering and lysosomal function, contributing to improved liver lipid handling and supporting phytocannabinoids as promising MASLD therapeutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70387","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:53:19Z","timestamp":1772992399000},"page":"3173-3194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cannabidiol and cannabigerol ameliorate steatotic liver disease via phosphocreatine buffering and lysosomal restoration"],"prefix":"10.1111","volume":"183","author":[{"given":"Radka","family":"Ko\u010dvarov\u00e1","sequence":"first","affiliation":[{"name":"Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahar","family":"Azar","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Agranovich","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Metabolomics Center, B. 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