{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:49:52Z","timestamp":1792590592254,"version":"4.5.0"},"reference-count":38,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473612"],"award-info":[{"award-number":["82473612"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515010779"],"award-info":[{"award-number":["2025A1515010779"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Top Talent Project in Special Support Plan for Training High-level Talents in Guangdong","award":["0720240244"],"award-info":[{"award-number":["0720240244"]}]},{"name":"Science Foundation of Guangdong Second Provincial General Hospital","award":["YY2018-002"],"award-info":[{"award-number":["YY2018-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Stevioside is a widely used natural non-nutritive sweetener derived from Stevia rebaudiana; however, its effects on MASLD and the underlying molecular mechanisms remain unclear. This study aimed to elucidate the effects and mechanisms of stevioside on MASLD, based on the high-fat diet-induced mice model and palmitic acid-treated hepatocyte model. We found that stevioside significantly alleviated hepatic steatosis in MASLD mice and reduced plasma ALT and AST levels and hepatic triglyceride and total cholesterol. In palmitic acid-induced hepatocytes, stevioside significantly reduced intracellular lipid droplet content and upregulated the protein levels of p-AMPK, PPAR\u03b1, and EHHADH. Pharmacological inhibition of AMPK and PPAR\u03b1 revealed that stevioside regulated PPAR\u03b1 expression and downstream EHHADH expression in an AMPK-dependent manner. To conclude, stevioside significantly improved hepatic steatosis in MASLD by activating the AMPK\/PPAR\u03b1\/EHHADH pathway, potentially generating novel evidence to help control the escalating disease burden of MASLD from the perspective of natural sweetener.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05606","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:01:33Z","timestamp":1791799293000},"page":"32309-32317","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Stevioside\non Hepatic Steatosis in Metabolic\nDysfunction-Associated Steatotic Liver Disease"],"prefix":"10.1021","volume":"74","author":[{"given":"Changfa","family":"Zhang","sequence":"first","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University , , ,","place":["Guangzhou, China, 510317"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University , , ,","place":["Guangzhou, China, 510317"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangjun","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University , , ,","place":["Guangzhou, China, 510317"]},{"name":"Guangdong University of Technology , , ,","place":["Guangzhou, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoting","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University , , ,","place":["Guangzhou, China, 510317"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Kang","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , ,","place":["Guangzhou, China, 510310"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoguan","family":"Peng","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University , , ,","place":["Guangzhou, China, 510170"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1184-1791","authenticated-orcid":true,"given":"Guowei","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University , , ,","place":["Guangzhou, China, 510317"]},{"name":"McMaster University , ,","place":["Hamilton, Canada, L8N 4A6"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"issue":"1","key":"2026102109071182700_cit1","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.cmet.2023.12.013","article-title":"Serine synthesis via reversed SHMT2 activity drives\nglycine depletion and acetaminophen hepatotoxicity in MASLD","volume":"36","author":"Ghrayeb","year":"2024","journal-title":"Cell Metab."},{"issue":"1","key":"2026102109071182700_cit2","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1186\/s10020-024-01003-6","article-title":"Lycorine\nameliorates liver steatosis, oxidative stress, ferroptosis and intestinal\nhomeostasis imbalance in MASLD mice","volume":"30","author":"Wang","year":"2024","journal-title":"Mol. Med."},{"issue":"7","key":"2026102109071182700_cit3","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms\nof NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"issue":"15","key":"2026102109071182700_cit4","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1097\/CM9.0000000000003629","article-title":"MASLD development: From molecular pathogenesis toward\ntherapeutic\nstrategies","volume":"138","author":"Yang","year":"2025","journal-title":"Chin. Med. J."},{"key":"2026102109071182700_cit5","doi-asserted-by":"publisher","first-page":"106786","DOI":"10.1016\/j.phrs.2023.106786","article-title":"Roles of the peroxisome\nproliferator-activated receptors (PPARs) in the pathogenesis of nonalcoholic\nfatty liver disease (NAFLD)","volume":"192","author":"Qiu","year":"2023","journal-title":"Pharmacol. Res."},{"key":"2026102109071182700_cit6","doi-asserted-by":"publisher","first-page":"107791","DOI":"10.1016\/j.pharmthera.2020.107791","article-title":"Peroxisome proliferator-activated\nreceptors in the pathogenesis and therapies of liver fibrosis","volume":"222","author":"Han","year":"2021","journal-title":"Pharmacol. Ther."},{"issue":"21","key":"2026102109071182700_cit7","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202415846","article-title":"Asprosin-FABP5 Interaction Modulates Mitochondrial\nFatty Acid Oxidation through PPAR\u03b1 Contributing to MASLD Development","volume":"12","author":"Yu","year":"2025","journal-title":"Adv. Sci."},{"issue":"1","key":"2026102109071182700_cit8","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1186\/s12889-023-17223-0","article-title":"Association between diet soft drink consumption and metabolic dysfunction-associated\nsteatotic liver disease: findings from the NHANES","volume":"23","author":"Wu","year":"2023","journal-title":"BMC Public Health"},{"key":"2026102109071182700_cit9","doi-asserted-by":"publisher","first-page":"1638147","DOI":"10.3389\/fphar.2025.1638147","article-title":"Stevia rebaudiana Bertoni\nas a sweet herbal medicine:\ntraditional uses, potential applications, and future development","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"2026102109071182700_cit10","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.jot.2022.05.005","article-title":"Stevioside attenuates osteoarthritis\nvia regulating Nrf2\/HO-1\/NF-\u03baB pathway","volume":"38","author":"Wu","year":"2023","journal-title":"J. Orthop. Translat."},{"issue":"1","key":"2026102109071182700_cit11","doi-asserted-by":"publisher","first-page":"2452241","DOI":"10.1080\/19490976.2025.2452241","article-title":"Stevioside mitigates metabolic dysregulation in offspring induced\nby maternal high-fat diet: the role of gut microbiota-driven thermogenesis","volume":"17","author":"Ye","year":"2025","journal-title":"Gut Microbes."},{"issue":"5","key":"2026102109071182700_cit12","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.3390\/antiox12051070","article-title":"Stevioside Improves Antioxidant Capacity and Intestinal Barrier Function\nwhile Attenuating Inflammation and Apoptosis by Regulating the NF-\u03baB\/MAPK\nPathways in Diquat-Induced Oxidative Stress of IPEC-J2 Cells","volume":"12","author":"Xu","year":"2023","journal-title":"Antioxidants"},{"issue":"1","key":"2026102109071182700_cit13","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s10068-021-01012-9","article-title":"Occurrence\nand risk characterization of non-nutritive sweeteners in selected\nfood products from Korea","volume":"31","author":"Kang","year":"2022","journal-title":"Food Sci. Biotechnol."},{"issue":"1","key":"2026102109071182700_cit14","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s13197-016-2450-2","article-title":"Physico-chemical and\nsensory characteristics of steviolbioside synthesized from stevioside\nand its application in fruit drinks and food","volume":"54","author":"Khattab","year":"2017","journal-title":"J. Food Sci. Technol."},{"key":"2026102109071182700_cit15","doi-asserted-by":"publisher","first-page":"14733","DOI":"10.1038\/ncomms14733","article-title":"Steviol glycosides enhance pancreatic beta-cell\nfunction and taste sensation by potentiation of TRPM5 channel activity","volume":"8","author":"Philippaert","year":"2017","journal-title":"Nat. Commun."},{"issue":"21","key":"2026102109071182700_cit16","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.70190","article-title":"Stevioside\nImproves Liver Insulin\nResistance in Prediabetic Mice via IRS1\/PI3K\/AKT Signaling Pathway","volume":"69","author":"Zhang","year":"2025","journal-title":"Mol. Nutr. Food Res."},{"issue":"20","key":"2026102109071182700_cit17","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.3390\/nu16203475","article-title":"(E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone,\na Major Homoisoflavonoid, Attenuates Free Fatty Acid-Induced Hepatic\nSteatosis by Activating AMPK and PPAR\u03b1 Pathways in HepG2 Cells","volume":"16","author":"Park","year":"2024","journal-title":"Nutrients"},{"key":"2026102109071182700_cit18","doi-asserted-by":"publisher","first-page":"156458","DOI":"10.1016\/j.metabol.2025.156458","article-title":"Imeglimin ameliorates MASLD by targeting PEN2 to activate\nAMPK pathway","volume":"175","author":"Li","year":"2026","journal-title":"Metab., Clin. 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Hepatol."},{"issue":"6","key":"2026102109071182700_cit25","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.3390\/ijms21062061","article-title":"PPARs as Metabolic\nRegulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice","volume":"21","author":"Wang","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"2026102109071182700_cit26","doi-asserted-by":"publisher","first-page":"5451","DOI":"10.1038\/s41467-023-41061-8","article-title":"Hyodeoxycholic\nacid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated\nPPAR\u03b1 nucleus-cytoplasm shuttling","volume":"14","author":"Zhong","year":"2023","journal-title":"Nat.\nCommun."},{"issue":"7","key":"2026102109071182700_cit27","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1194\/jlr.M024463","article-title":"Peroxisomal\nL-bifunctional enzyme\n(Ehhadh) is essential for the production of medium-chain dicarboxylic\nacids","volume":"53","author":"Houten","year":"2012","journal-title":"J. Lipid Res."},{"issue":"14","key":"2026102109071182700_cit28","doi-asserted-by":"publisher","first-page":"5631","DOI":"10.1007\/s00018-021-03869-9","article-title":"Murine deficiency\nof peroxisomal L-bifunctional protein\n(EHHADH) causes medium-chain 3-hydroxydicarboxylic aciduria and perturbs\nhepatic cholesterol homeostasis","volume":"78","author":"Ranea-Robles","year":"2021","journal-title":"Cell. Mol.\nLife Sci."},{"issue":"6","key":"2026102109071182700_cit29","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1111\/bcpt.13194","article-title":"Stevioside\ninhibits experimental fibrosis by down-regulating\nprofibrotic Smad pathways and blocking hepatic stellate cell activation","volume":"124","author":"Casas-Grajales","year":"2019","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"issue":"3","key":"2026102109071182700_cit30","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.aohep.2018.10.002","article-title":"An aqueous\nextract\nof Stevia rebaudiana variety Morita II prevents liver damage in a\nrat model of cirrhosis that mimics the human disease","volume":"18","author":"Ramos-Tovar","year":"2019","journal-title":"Ann. Hepatol."},{"key":"2026102109071182700_cit31","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.17179\/excli2021-4211","article-title":"Natural sweetener\nStevia rebaudiana: Functionalities, health benefits and potential\nrisks","volume":"20","author":"Peteliuk","year":"2021","journal-title":"Excli J."},{"issue":"2","key":"2026102109071182700_cit32","doi-asserted-by":"publisher","DOI":"10.1002\/SMMD.20240010","article-title":"Stevioside protects\nagainst acute kidney injury by inhibiting gasdermin D pathway","volume":"3","author":"Qiao","year":"2024","journal-title":"Smart Med."},{"issue":"Suppl","key":"2026102109071182700_cit33","doi-asserted-by":"publisher","first-page":"S32","DOI":"10.3350\/cmh.2024.0431","article-title":"Epidemiology of metabolic dysfunction-associated\nsteatotic liver disease","volume":"31","author":"Younossi","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"issue":"5","key":"2026102109071182700_cit34","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","article-title":"AASLD Practice\nGuidance on the clinical assessment and management of nonalcoholic\nfatty liver disease","volume":"77","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"2026102109071182700_cit35","doi-asserted-by":"publisher","first-page":"1710267","DOI":"10.3389\/fnut.2025.1710267","article-title":"Identification of the role of sugar-sweetened\nbeverages in the progression of a murine metabolic dysfunction-associated\nsteatotic liver disease model","volume":"12","author":"Li","year":"2025","journal-title":"Front. Nutr."},{"key":"2026102109071182700_cit36","doi-asserted-by":"publisher","first-page":"103499","DOI":"10.1016\/j.redox.2025.103499","article-title":"Caffeine ameliorates\nmetabolic-associated steatohepatitis by rescuing hepatic Dusp9","volume":"80","author":"Xin","year":"2025","journal-title":"Redox Biol."},{"issue":"2","key":"2026102109071182700_cit37","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3390\/biology10020082","article-title":"Long-Term\nAspartame Administration Leads to Fibrosis, Inflammasome Activation,\nand Gluconeogenesis Impairment in the Liver of Mice","volume":"10","author":"Finamor","year":"2021","journal-title":"Biology"},{"issue":"2","key":"2026102109071182700_cit38","doi-asserted-by":"publisher","first-page":"192","DOI":"10.3390\/medicina61020192","article-title":"Effects of Selected Food Additives\non the Gut Microbiome and Metabolic Dysfunction-Associated Steatotic\nLiver Disease (MASLD)","volume":"61","author":"Jarmakiewicz-Czaja","year":"2025","journal-title":"Medicina"}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c05606","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/41\/32309\/68817795\/acs.jafc.6c05606.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/41\/32309\/68817795\/acs.jafc.6c05606.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:29:43Z","timestamp":1792589383000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/41\/32309\/5448879\/The-Effect-of-Stevioside-on-Hepatic-Steatosis-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":38,"journal-issue":{"issue":"41","published-online":{"date-parts":[[2026,10,12]]},"published-print":{"date-parts":[[2026,10,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c05606","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]}}}