{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:31:50Z","timestamp":1785407510847,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008092","name":"Science and Technology Bureau of Jinhua City","doi-asserted-by":"crossref","award":["2026-3-009"],"award-info":[{"award-number":["2026-3-009"]}],"id":[{"id":"10.13039\/501100008092","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008092","name":"Science and Technology Bureau of Jinhua City","doi-asserted-by":"crossref","award":["2024-3-032"],"award-info":[{"award-number":["2024-3-032"]}],"id":[{"id":"10.13039\/501100008092","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2026-3-009"],"award-info":[{"award-number":["2026-3-009"]}],"id":[{"id":"https:\/\/ror.org\/016p59286","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2024-3-032"],"award-info":[{"award-number":["2024-3-032"]}],"id":[{"id":"https:\/\/ror.org\/016p59286","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: The development of non-alcoholic fatty liver disease (NAFLD) is closely linked to oxidative stress and inflammation. Aerobic exercise has been shown to improve NAFLD, although its underlying mechanisms remain incompletely understood. This study utilized ApoE-\/- mice to investigate the role of Sestrin2 in aerobic exercise-induced amelioration of NAFLD. Methods: Random assignment of C57BL\/6J and ApoE-\/- mice yielded four groups: C (control), CE (aerobic exercise), AS (ApoE-\/- control), and AE (ApoE-\/- aerobic exercise). Aerobic exercise lasting 12 weeks was administered to the CE and AE groups. Serum biomarkers were analyzed by ELISA, liver tissue morphology was assessed via HE and ORO staining, and macrophage polarization was evaluated through immunofluorescence. Additionally, mRNA and protein expression levels were measured by qPCR and Western blot. Results: Aerobic exercise reduced liver wet weight, lipid accumulation, and steatosis in ApoE-\/- mice. Aerobic exercise attenuates hepatic oxidative stress, and upregulated the expression of regulation oxidative stress related gene and proteins of Nrf2, HO-1, CAT, and SOD1 in ApoE-\/- mice. Aerobic exercise promoted a shift in macrophage polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype in the liver, and significantly reduced TNF-\u03b1 and IL-1\u03b2 levels, accompanied by upregulation of Sestrin2 expression, enhanced AMPK phosphorylation, inhibited mTORC1 in the liver. Conclusions: These findings suggest that aerobic exercise alleviates oxidative stress and inflammation in NAFLD, with Sestrin2 activation playing a central role.<\/jats:p>","DOI":"10.3390\/metabo16040285","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:10:44Z","timestamp":1776787844000},"page":"285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aerobic Exercise Alleviates Oxidative Stress and Inflammation to Attenuate High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in ApoE-\/- Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Liang","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengting","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Weng","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingbo","family":"Li","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8258-7911","authenticated-orcid":false,"given":"Lifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"ITC65","DOI":"10.7326\/AITC201811060","article-title":"Nonalcoholic fatty liver disease","volume":"169","author":"Wang","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.freeradbiomed.2020.02.025","article-title":"Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease","volume":"152","author":"Chen","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1053\/j.gastro.2019.11.311","article-title":"Mechanisms of fibrosis development in nonalcoholic steatohepatitis","volume":"158","author":"Schwabe","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.jhep.2023.01.024","article-title":"An adipocentric perspective on the development and progression of non-alcoholic fatty liver disease","volume":"78","author":"Lee","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12944-025-02483-z","article-title":"Fucoidan ameliorates lipid accumulation, oxidative stress, and NF-\u03baB-mediated inflammation by regulating the PI3K\/AKT\/Nrf2 signaling pathway in a free fatty acid-induced NAFLD spheroid model","volume":"24","author":"Chu","year":"2025","journal-title":"Lipids Health Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1159\/000484060","article-title":"Recent insights into the biological functions of sestrins in health and disease","volume":"43","author":"Wang","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.bbrc.2020.03.032","article-title":"Liraglutide ameliorates obesity-related nonalcoholic fatty liver disease by regulating Sestrin2-mediated Nrf2\/HO-1 pathway","volume":"525","author":"Han","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/s12276-022-00829-6","article-title":"The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights","volume":"54","author":"Xiang","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ma, Y., Zhang, G., Kuang, Z., Xu, Q., Ye, T., Li, X., Qu, N., Han, F., Kan, C., and Sun, X. (2022). Empagliflozin activates Sestrin2-mediated AMPK\/mTOR pathway and ameliorates lipid accumulation in obesity-related nonalcoholic fatty liver disease. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.944886"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Park, S.-J., Garcia Diaz, J., Um, E., and Hahn, Y.S. (2023). Major roles of kupffer cells and macrophages in NAFLD development. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1150118"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1900768","DOI":"10.1002\/mnfr.201900768","article-title":"Regulation of adipocyte and macrophage functions by mTORC1 and 2 in metabolic diseases","volume":"65","author":"Festuccia","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105796","DOI":"10.1016\/j.phrs.2021.105796","article-title":"Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization","volume":"172","author":"Wu","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.freeradbiomed.2014.11.002","article-title":"Role of sestrin2 in the regulation of proinflammatory signaling in macrophages","volume":"78","author":"Yang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yang, K., Xu, C., Zhang, Y., He, S., and Li, D. (2017). Sestrin2 suppresses classically activated macrophages-mediated inflammatory response in myocardial infarction through inhibition of mTORC1 signaling. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00728"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yang, Y., Li, X., Liu, Z., Ruan, X., Wang, H., Zhang, Q., Cao, L., Song, L., Chen, Y., and Sun, Y. (2022). Moderate treadmill exercise alleviates NAFLD by regulating the biogenesis and autophagy of lipid droplet. Nutrients, 14.","DOI":"10.3390\/nu14224910"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Xu, Z., Qin, Y., Lv, B., Tian, Z., and Zhang, B. (2022). Effects of moderate-intensity continuous training and high-intensity interval training on testicular oxidative stress, apoptosis and m6A methylation in obese male mice. Antioxidants, 11.","DOI":"10.3390\/antiox11101874"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"166792","DOI":"10.1016\/j.bbadis.2023.166792","article-title":"Exercise ameliorates chronic inflammatory response induced by high-fat diet via Sestrin2 in an Nrf2-dependent manner","volume":"1869","author":"Liu","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1093\/gerona\/glab029","article-title":"Aerobic Exercise Improves Mitochondrial Function in Sarcopenia Mice Through Sestrin2 in an AMPK\u03b12-Dependent Manner","volume":"76","author":"Liu","year":"2021","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"C164","DOI":"10.1152\/ajpcell.00344.2021","article-title":"Aerobic exercise and resistance exercise alleviate skeletal muscle atrophy through IGF-1\/IGF-1R-PI3K\/Akt pathway in mice with myocardial infarction","volume":"322","author":"Feng","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.20463\/pan.2023.0013","article-title":"Exogenous lactate intake immediately after endurance exercise increases time to exhaustion in VO2max measurements in mice","volume":"27","author":"Kyun","year":"2023","journal-title":"Phys. Act. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12931","DOI":"10.1038\/srep12931","article-title":"Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis","volume":"5","author":"Schierwagen","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nasiri-Ansari, N., Nikolopoulou, C., Papoutsi, K., Kyrou, I., Mantzoros, C.S., Kyriakopoulos, G., Chatzigeorgiou, A., Kalotychou, V., Randeva, M.S., and Chatha, K. (2021). Empagliflozin attenuates non-alcoholic fatty liver disease (NAFLD) in high fat diet fed ApoE(-\/-) mice by activating autophagy and reducing ER stress and apoptosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020818"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.orcp.2017.01.004","article-title":"Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice","volume":"12","author":"Ghareghani","year":"2018","journal-title":"Obes. Res. Clin. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e14926","DOI":"10.14814\/phy2.14926","article-title":"The effect of endurance training on non-alcoholic fatty liver disease in mice","volume":"9","author":"Melo","year":"2021","journal-title":"Physiol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.bbrc.2022.03.008","article-title":"Aerobic exercise improves non-alcoholic fatty liver disease by down-regulating the protein expression of the CNPY2-PERK pathway","volume":"603","author":"Li","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s11892-015-0607-4","article-title":"Nonalcoholic fatty liver disease and type 2 diabetes: Common pathophysiologic mechanisms","volume":"15","author":"Saponaro","year":"2015","journal-title":"Curr. Diab. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.amjms.2016.11.002","article-title":"Aerobic exercise suppresses atherosclerosis through adiponectin-nuclear transcription factor \u03baB pathway in apolipoprotein E-deficient mice","volume":"353","author":"Wu","year":"2017","journal-title":"Am. J. Med. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.semcdb.2020.04.011","article-title":"Hepatic lipid droplet homeostasis and fatty liver disease","volume":"108","author":"Seebacher","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1172\/JCI86695","article-title":"Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver","volume":"126","author":"Satapati","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Arroyave-Ospina, J.C., Wu, Z., Geng, Y., and Moshage, H. (2021). Role of oxidative stress in the pathogenesis of non-alcoholic fatty liver disease: Implications for prevention and therapy. Antioxidants, 10.","DOI":"10.3390\/antiox10020174"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12944-023-01798-z","article-title":"Exercise activates Sirt1-mediated Drp1 acetylation and inhibits hepatocyte apoptosis to improve nonalcoholic fatty liver disease","volume":"22","author":"Hu","year":"2023","journal-title":"Lipids Health Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Xiong, Y., Peng, Q., Cao, C., Xu, Z., and Zhang, B. (2021). Effect of Different Exercise Methods on Non-Alcoholic Fatty Liver Disease: A Meta-Analysis and Meta-Regression. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18063242"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Liu, X., Zhong, Y., Guo, Y., Xu, J., Wang, S., Liu, Y., Lv, Y., and Zheng, X. (2025). Treadmill Exercise-Induced RNA m6A Methylation Modification in the Prevention of High-Fat Diet-Induced MASLD in Mice. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125810"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"109083","DOI":"10.1016\/j.isci.2024.109083","article-title":"Chronic exercise improves hepatic acylcarnitine handling","volume":"27","author":"Hinkley","year":"2024","journal-title":"iScience"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.freeradbiomed.2025.02.017","article-title":"Regular exercise alleviates metabolic dysfunction-associated steatohepatitis through rescuing mitochondrial oxidative stress and dysfunction in liver","volume":"230","author":"Lin","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109086","DOI":"10.1016\/j.cbi.2020.109086","article-title":"Sestrin2 overexpression alleviates hydrogen peroxide-induced apoptosis and oxidative stress in retinal ganglion cells by enhancing Nrf2 activation via Keap1 downregulation","volume":"324","author":"Fan","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.freeradbiomed.2024.02.003","article-title":"Sestrin2 reduces ferroptosis via the Keap1\/Nrf2 signaling pathway after intestinal ischemia-reperfusion","volume":"214","author":"Zhang","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"146948","DOI":"10.1016\/j.brainres.2020.146948","article-title":"Sestrin2 promotes angiogenesis to alleviate brain injury by activating Nrf2 through regulating the interaction between p62 and Keap1 following photothrombotic stroke in rats","volume":"1745","author":"Li","year":"2020","journal-title":"Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.cmet.2012.12.002","article-title":"Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage","volume":"17","author":"Bae","year":"2013","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1139\/apnm-2021-0241","article-title":"Exercise improves lipid metabolism disorders induced by high-fat diet in a SESN2\/JNK-independent manner","volume":"46","author":"Wang","year":"2021","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117958","DOI":"10.1016\/j.lfs.2020.117958","article-title":"Exercise protects against ethanol-induced damage in rat heart and liver through the inhibition of apoptosis and activation of Nrf2\/Keap-1\/HO-1 pathway","volume":"256","author":"Fathi","year":"2020","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.mam.2007.09.004","article-title":"Oxidative mechanisms in the pathogenesis of alcoholic liver disease","volume":"29","author":"Albano","year":"2008","journal-title":"Mol. Asp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s11011-022-01135-w","article-title":"Castor1 overexpression regulates microglia M1\/M2 polarization via inhibiting mTOR pathway","volume":"38","author":"Hu","year":"2023","journal-title":"Metab. Brain Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/978-1-62703-128-8_14","article-title":"Generation and characterization of murine alternatively activated macrophages","volume":"946","author":"Weisser","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1042\/CS20110366","article-title":"Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice","volume":"122","author":"Maina","year":"2012","journal-title":"Clin. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"133","DOI":"10.5625\/lar.2018.34.4.133","article-title":"The role of hepatic macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"34","author":"Cha","year":"2018","journal-title":"Lab. Anim. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1038\/s41380-024-02464-1","article-title":"Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1\/M2 polarization through adiponectin\/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress","volume":"29","author":"Liu","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1038\/ncomms3834","article-title":"The TSC-mTOR pathway regulates macrophage polarization","volume":"4","author":"Byles","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.cell.2008.06.028","article-title":"p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling","volume":"134","author":"Budanov","year":"2008","journal-title":"Cell"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/4\/285\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:19:51Z","timestamp":1776917991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/4\/285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["metabo16040285"],"URL":"https:\/\/doi.org\/10.3390\/metabo16040285","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]}}}