{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:34Z","timestamp":1785430474530,"version":"3.56.0"},"reference-count":79,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LIPOVEXA S.r.l"},{"name":"School of Diagnostic and Therapeutic Sciences and the Curtin Medical Research Institute, Curtin University"},{"id":[{"id":"https:\/\/ror.org\/02n415q13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pharmacological treatment of metabolic-dysfunction-associated steatohepatitis remains challenging due to its complex pathophysiology. The endocannabinoidome (eCB) has emerged as a promising therapeutic target given its central role in energy homeostasis and its pharmacological tractability. Western-style diets high in fat and sugar exacerbate metabolic liver disease, highlighting the need for effective interventions. Here, we investigated the therapeutic potential of cannabinoid combinations targeting the eCB\u2013liver axis in a Western diet-induced model of metabolic dysfunction. Two weeks of treatment reduced body weight, improved glycaemic control, and ameliorated liver pathology. These effects were accompanied by decreased liver weight, improved liver enzyme profiles, and reduced histological features of steatosis and injury. Overall, these findings suggest that modulation of the eCB system can induce acute improvements in metabolic and hepatic parameters under conditions of diet-induced metabolic stress. These results support further investigation into the eCB system as a therapeutic target, particularly to elucidate underlying mechanisms and longer-term effects.<\/jats:p>","DOI":"10.3390\/ijms27114872","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:09:07Z","timestamp":1779970147000},"page":"4872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acute Effects of Cannabinoid Combination Therapies in a Western Diet-Induced Murine Model of Metabolic Liver Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Jerome","family":"Lian","sequence":"first","affiliation":[{"name":"Diagnostic and Therapeutic Sciences and Curtin Medical Research Institute, Faculty of Health Sciences, Curtin University, Perth, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6803-9858","authenticated-orcid":false,"given":"Mohan","family":"Patil","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Perth, WA 6000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-3499","authenticated-orcid":false,"given":"Ricky R.","family":"Lareu","sequence":"additional","affiliation":[{"name":"Diagnostic and Therapeutic Sciences and Curtin Medical Research Institute, Faculty of Health Sciences, Curtin University, Perth, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-7235","authenticated-orcid":false,"given":"Marco","family":"Falasca","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Perth, WA 6000, Australia"},{"name":"Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43125 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/S2468-1253(24)00193-6","article-title":"Natural history and progression of metabolic dysfunction-associated steatotic liver disease","volume":"9","author":"Shang","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12944-024-02108-x","article-title":"Updated mechanisms of MASLD pathogenesis","volume":"23","author":"Li","year":"2024","journal-title":"Lipids Health Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.3350\/cmh.2024.0431","article-title":"Epidemiology of metabolic dysfunction-associated steatotic liver disease","volume":"31","author":"Younossi","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.tem.2024.02.007","article-title":"Current status and future trends of the global burden of MASLD","volume":"35","author":"Miao","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1080\/1744666X.2023.2294046","article-title":"The pathophysiology of MASLD: An immunometabolic perspective","volume":"20","author":"Grabherr","year":"2024","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.cnc.2022.04.004","article-title":"Hepatocellular Carcinoma","volume":"34","author":"Gilles","year":"2022","journal-title":"Crit. Care Nurs. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1097\/HEP.0000000000000786","article-title":"Molecular mechanisms in MASLD\/MASH-related HCC","volume":"82","author":"Wang","year":"2025","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.7570\/jomes23052","article-title":"Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A State-of-the-Art Review","volume":"32","author":"Chan","year":"2023","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2445780","DOI":"10.1080\/07853890.2024.2445780","article-title":"Research advances in the diagnosis and treatment of MASLD\/MASH","volume":"57","author":"Wang","year":"2025","journal-title":"Ann. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106025","DOI":"10.1016\/j.phrs.2021.106025","article-title":"Modulatory role of the endocannabinoidome in the pathophysiology of the gastrointestinal tract","volume":"175","author":"Lian","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Falasca, V., and Falasca, M. (2022). Targeting the Endocannabinoidome in Pancreatic Cancer. Biomolecules, 12.","DOI":"10.3390\/biom12020320"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"210","DOI":"10.5152\/eurjrheum.2017.17025","article-title":"The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease","volume":"4","author":"Barrie","year":"2017","journal-title":"Eur. J. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Arifin, S.A., and Falasca, M. (2016). Lysophosphatidylinositol Signalling and Metabolic Diseases. Metabolites, 6.","DOI":"10.3390\/metabo6010006"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/hep.31290","article-title":"The L-\u03b1-Lysophosphatidylinositol\/G Protein-Coupled Receptor 55 System Induces the Development of Nonalcoholic Steatosis and Steatohepatitis","volume":"73","author":"Fondevila","year":"2021","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s11658-021-00276-7","article-title":"Targeting the GPR119\/incretin axis: A promising new therapy for metabolic-associated fatty liver disease","volume":"26","author":"Zhao","year":"2021","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, S., and Kim, J.K. (2024). The Role of Cannabidiol in Liver Disease: A Systemic Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042370"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"110040","DOI":"10.1016\/j.jnutbio.2025.110040","article-title":"Dietary cannabidiol oil mitigates metabolic dysfunction in mice with high-fat diet-induced obesity","volume":"146","author":"Sun","year":"2025","journal-title":"J. Nutr. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C1316","DOI":"10.1152\/ajpcell.00503.2025","article-title":"Cannabis improves metabolic dysfunction and macrophage signatures in obese mice","volume":"329","author":"VanderVeen","year":"2025","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5975","DOI":"10.1038\/s41598-026-36666-0","article-title":"Cannabidiol mitigates high-fat-diet-induced early-stage inflammation in two adipose tissue fat depots of Wistar rats","volume":"16","author":"Berk","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/sj.bjp.0707464","article-title":"GPR55: A new member of the cannabinoid receptor clan?","volume":"152","author":"Pertwee","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1038\/s41386-020-0667-2","article-title":"Adverse effects of cannabidiol: A systematic review and meta-analysis of randomized clinical trials","volume":"45","author":"Chesney","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature01921","article-title":"Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha","volume":"425","author":"Fu","year":"2003","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1111\/obr.12853","article-title":"The effects of oleoylethanolamide, an endogenous PPAR-\u03b1 agonist, on risk factors for NAFLD: A systematic review","volume":"20","author":"Tutunchi","year":"2019","journal-title":"Obes. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s11745-008-3217-y","article-title":"Biological functions and metabolism of oleoylethanolamide","volume":"43","author":"Thabuis","year":"2008","journal-title":"Lipids"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.2337\/db08-1237","article-title":"GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell","volume":"58","author":"Lauffer","year":"2009","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cmet.2008.08.005","article-title":"The lipid messenger OEA links dietary fat intake to satiety","volume":"8","author":"Schwartz","year":"2008","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plipres.2017.04.001","article-title":"Oleic acid-derived oleoylethanolamide: A nutritional science perspective","volume":"67","author":"Bowen","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.bbalip.2018.06.007","article-title":"Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119","volume":"1863","author":"Arifin","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105822","DOI":"10.1016\/j.phrs.2021.105822","article-title":"Pharmacological and structure-activity relationship studies of oleoyl-lysophosphatidylinositol synthetic mimetics","volume":"172","author":"Paternoster","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117077","DOI":"10.1016\/j.biopha.2024.117077","article-title":"Preclinical pharmacokinetics, pharmacodynamics, and toxicity of novel small-molecule GPR119 agonists to treat type-2 diabetes and obesity","volume":"177","author":"Patil","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"947","DOI":"10.2174\/1570159X17666190118143014","article-title":"Potential metabolic and behavioural roles of the putative endocannabinoid receptors GPR18, GPR55 and GPR119 in feeding","volume":"17","author":"Morales","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1007\/s00125-016-4108-z","article-title":"Metabolic effects of orally administered small-molecule agonists of GPR55 and GPR119 in multiple low-dose streptozotocin-induced diabetic and incretin-receptor-knockout mice","volume":"59","author":"McKillop","year":"2016","journal-title":"Diabetologia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"G304","DOI":"10.1152\/ajpgi.00275.2020","article-title":"GPCRs get fatty: The role of G protein-coupled receptor signaling in the development and progression of nonalcoholic fatty liver disease","volume":"320","author":"Kurtz","year":"2021","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100018","DOI":"10.1016\/j.pharmr.2024.100018","article-title":"Pharmacological treatment for metabolic dysfunction\u2013associated steatotic liver disease and related disorders: Current and emerging therapeutic options","volume":"77","author":"Zhang","year":"2025","journal-title":"Pharmacol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Machado, M.V., Michelotti, G.A., Xie, G., Almeida Pereira, T., Boursier, J., Bohnic, B., Guy, C.D., and Diehl, A.M. (2015). Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132315"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Syed-Abdul, M.M. (2024). Lipid Metabolism in Metabolic-Associated Steatotic Liver Disease (MASLD). Metabolites, 14.","DOI":"10.3390\/metabo14010012"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1586\/egh.11.8","article-title":"Hepatocellular ballooning in nonalcoholic steatohepatitis: The pathologist\u2019s perspective","volume":"5","author":"Lackner","year":"2011","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2017.12.036","article-title":"A High-fat, High-sugar \u2018Western\u2019 Diet Alters Dorsal Striatal Glutamate, Opioid, and Dopamine Transmission in Mice","volume":"372","author":"Fritz","year":"2018","journal-title":"Neuroscience"},{"key":"ref_39","first-page":"e76716","article-title":"Targeting Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Available and Future Pharmaceutical Options","volume":"17","author":"Koullias","year":"2025","journal-title":"Cureus"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3748\/wjg.v27.i8.677","article-title":"G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment","volume":"27","author":"Yang","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e70576","DOI":"10.1111\/liv.70576","article-title":"Targeting the LPI\/GPR55 Axis in MAFLD and MASH: Novel Insights, Therapeutic Strategies and Future Directions","volume":"46","author":"Lian","year":"2026","journal-title":"Liver Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1210\/en.2010-1047","article-title":"GPR119 regulates murine glucose homeostasis through incretin receptor-dependent and independent mechanisms","volume":"152","author":"Flock","year":"2011","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Im, D.-S. (2021). GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031034"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: Pathophysiological basis for therapy","volume":"72","author":"Albillos","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.3748\/wjg.v30.i23.2964","article-title":"Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease","volume":"30","author":"Kalinowski","year":"2024","journal-title":"World J. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S0140-6736(04)17663-0","article-title":"Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis","volume":"365","author":"Pereira","year":"2005","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Clemente-Su\u00e1rez, V.J., Beltr\u00e1n-Velasco, A.I., Redondo-Fl\u00f3rez, L., Mart\u00edn-Rodr\u00edguez, A., and Tornero-Aguilera, J.F. (2023). Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review. Nutrients, 15.","DOI":"10.3390\/nu15122749"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1530\/JOE-11-0166","article-title":"A role for the putative cannabinoid receptor GPR55 in the islets of Langerhans","volume":"211","author":"Rafacho","year":"2011","journal-title":"J. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1111\/bph.14387","article-title":"Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis","volume":"175","author":"Hill","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.bbi.2018.11.017","article-title":"Activation of GPR55 induces neuroprotection of hippocampal neurogenesis and immune responses of neural stem cells following chronic, systemic inflammation","volume":"76","author":"Hill","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1089\/can.2023.0285","article-title":"Hepatoprotective Effect of Cannabidiol on the Progression of Experimental Hepatic Cirrhosis in Rats","volume":"10","year":"2025","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Rafailovska, E., Xhemaili, E., Naumovska, Z., Gigopulu, O., Miova, B., Suturkova, L., and Stefkov, G. (2025). Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical Studies. Pharmaceuticals, 18.","DOI":"10.3390\/ph18040446"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Atalay, S., Jarocka-Karpowicz, I., and Skrzydlewska, E. (2020). Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants, 9.","DOI":"10.3390\/antiox9010021"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"J\u00eetc\u0103, G., \u0150sz, B.E., Vari, C.E., Rusz, C.-M., Tero-Vescan, A., and Pu\u0219ca\u0219, A. (2023). Cannabidiol: Bridge between Antioxidant Effect, Cellular Protection, and Cognitive and Physical Performance. Antioxidants, 12.","DOI":"10.3390\/antiox12020485"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bahari, H., Jazinaki, M.S., Aghakhani, L., Hatami, A., Rahnama, I., and Malekahmadi, M. (2025). Oleoylethanolamide supplementation on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1553288"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s00795-018-0200-4","article-title":"Combination of APD668, a G protein-coupled receptor 119 agonist with linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in a murine model of non-alcoholic steatohepatitis with diabetes","volume":"52","author":"Bahirat","year":"2019","journal-title":"Med. Mol. Morphol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.bcp.2009.04.024","article-title":"N-acylethanolamines, anandamide and food intake","volume":"78","author":"Hansen","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1096\/fj.15-273771","article-title":"GPR119: A promising target for nonalcoholic fatty liver disease","volume":"30","author":"Yang","year":"2016","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.jhep.2015.01.001","article-title":"Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis","volume":"62","author":"Silvestri","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Hegde, V.L., Nagarkatti, P.S., and Nagarkatti, M. (2011). Role of myeloid-derived suppressor cells in amelioration of experimental autoimmune hepatitis following activation of TRPV1 receptors by cannabidiol. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018281"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"del R\u00edo, C., Ruiz-Pino, F., Prados, M.E., Fiebich, B.L., Tena-Sempere, M., and Mu\u00f1oz, E. (2022). Cannabidiol markedly alleviates skin and liver fibrosis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.981817"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.2337\/db24-0370","article-title":"DA-1241, a GPR119 Agonist, Ameliorates Fatty Liver Through the Upregulation of TFEB-Mediated Autophagy","volume":"74","author":"Yoo","year":"2025","journal-title":"Diabetes"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1161\/ATVBAHA.118.311339","article-title":"Mechanism of Increased LDL (Low-Density Lipoprotein) and Decreased Triglycerides With SGLT2 (Sodium-Glucose Cotransporter 2) Inhibition","volume":"38","author":"Basu","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"117236","DOI":"10.1016\/j.atherosclerosis.2023.117236","article-title":"SGLT2-inhibition increases total, LDL, and HDL cholesterol and lowers triglycerides: Meta-analyses of 60 randomized trials, overall and by dose, ethnicity, and drug type","volume":"394","author":"Bechmann","year":"2024","journal-title":"Atherosclerosis"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neulet.2018.06.006","article-title":"Sub-chronic treatment with cannabidiol but not with URB597 induced a mild antidepressant-like effect in diabetic rats","volume":"682","author":"Chaves","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1111\/bcp.13710","article-title":"The pharmacokinetics and the pharmacodynamics of cannabinoids","volume":"84","author":"Lucas","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1080\/17512433.2022.2148655","article-title":"Cannabinoids and drug metabolizing enzymes: Potential for drug-drug interactions and implications for drug safety and efficacy","volume":"15","author":"Bardhi","year":"2022","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.phytochem.2015.04.007","article-title":"Minor oxygenated cannabinoids from high potency Cannabis sativa L.","volume":"117","author":"Ahmed","year":"2015","journal-title":"Phytochemistry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/13543784.2024.2321271","article-title":"GPR119 agonists for type 2 diabetes: Past failures and future hopes for preclinical and early phase candidates","volume":"33","author":"Hryciw","year":"2024","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4093\/dmj.2021.0056","article-title":"DA-1241, a Novel GPR119 Agonist, Improves Hyperglycaemia by Inhibiting Hepatic Gluconeogenesis and Enhancing Insulin Secretion in Diabetic Mice","volume":"46","author":"Kim","year":"2022","journal-title":"Diabetes Metab. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"88","DOI":"10.2174\/1871524911313010010","article-title":"Brain molecules and appetite: The case of oleoylethanolamide","volume":"13","year":"2013","journal-title":"Cent. Nerv. Syst. Agents Med. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3945\/an.113.003798","article-title":"PPAR-\u03b1 as a Key Nutritional and Environmental Sensor for Metabolic Adaptation","volume":"4","author":"Contreras","year":"2013","journal-title":"Adv. Nutr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.physbeh.2015.03.029","article-title":"Factors influencing individual variability in high fat diet-induced weight gain in out-bred MF1 mice","volume":"144","author":"Vaanholt","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Flessa, C.M., Nasiri-Ansari, N., Kyrou, I., Leca, B.M., Lianou, M., Chatzigeorgiou, A., Kaltsas, G., Kassi, E., and Randeva, H.S. (2022). Genetic and Diet-Induced Animal Models for Non-Alcoholic Fatty Liver Disease (NAFLD) Research. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415791"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Carreres, L., J\u00edlkov\u00e1, Z.M., Vial, G., Marche, P.N., Decaens, T., and Lerat, H. (2021). Modeling Diet-Induced NAFLD and NASH in Rats: A Comprehensive Review. Biomedicines, 9.","DOI":"10.3390\/biomedicines9040378"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Liang, W., Menke, A.L., Driessen, A., Koek, G.H., Lindeman, J.H., Stoop, R., Havekes, L.M., Kleemann, R., and van den Hoek, A.M. (2014). Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115922"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1007\/s10620-016-4062-0","article-title":"Histological Assessment of NAFLD","volume":"61","author":"Bedossa","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"24601","DOI":"10.1038\/s41598-025-07540-2","article-title":"Valproate independently activates Snf1, inhibits TORC1, and induces repression of INO1 transcription by increasing nuclear localization of Opi1","volume":"15","author":"Case","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Furukawa, T., Yamane, F., Okumura, T., Miyazaki, T., and Tsutsui, N. (2025). The Effects of Eyestalk Ablation on the Androgenic Gland and the Male Reproductive Organs in the Kuruma Prawn Marsupenaeus japonicus. 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