{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:18:07Z","timestamp":1787897887178,"version":"build-2784847793"},"reference-count":79,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The health benefits of tomato consumption may derive from bioactive compounds other than lycopene in tomatoes. 15\u2010\n                    <jats:italic>Cis<\/jats:italic>\n                    \u2010phytoene, a colorless precursor of lycopene abundant in tomatoes, has not been well studied for its biological activity. We investigated whether dietary 15\u2010\n                    <jats:italic>cis<\/jats:italic>\n                    \u2010phytoene protects against metabolic dysfunction\u2010associated steatotic liver disease (MASLD) and whether this protection depends on the carotenoid cleavage enzymes, beta\u2010carotene\u201015,15\u2019\u2010oxygenase 1 (BCO1) and beta\u2010carotene\u20109\u2019,10\u2019\u2010oxygenase (BCO2). Wild\u2010type (WT) and BCO1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \/BCO2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    double knock\u2010out (DKO) mice were fed a high\u2010refined carbohydrate diet (HRCD) with or without 15\u2010\n                    <jats:italic>cis<\/jats:italic>\n                    \u2010phytoene supplementation for 24 weeks. 15\u2010\n                    <jats:italic>Cis<\/jats:italic>\n                    \u2010phytoene supplementation markedly increased 15\u2010\n                    <jats:italic>cis<\/jats:italic>\n                    and all\u2010\n                    <jats:italic>trans<\/jats:italic>\n                    phytoene concentrations in intestine, liver, and serum, and significantly attenuated HRCD\u2010induced MASLD in WT mice. The protective effects of phytoene on MASLD in WT mice were associated with increased hepatic mRNA and protein levels of SIRT1, PGC1\u03b1, and PPAR\u03b1; enhanced AMPK and ACC phosphorylation; and upregulated fatty acid oxidation genes, but not with the gut microbiota composition. Despite much higher phytoene accumulation in the liver and serum, phytoene did not exhibit protection against HRCD\u2010induced MASLD in DKO mice. Phytoene is a biologically active compound that contributes to the benefits of tomato consumption against MASLD. Its protective effects are likely mediated by cleavage metabolites through BCO1\/BCO2.\n                  <\/jats:p>","DOI":"10.1002\/mnfr.70596","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:43:21Z","timestamp":1787553801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phytoene, a Precursor of Lycopene in Tomatoes, Protects Against Metabolic Dysfunction\u2010Associated Steatotic Liver Disease in Mice"],"prefix":"10.1002","volume":"70","author":[{"given":"Na Youn","family":"Lee","sequence":"first","affiliation":[{"name":"Jean Mayer USDA Human Nutrition Research Center On Aging at Tufts University Boston Massachusetts USA"},{"name":"Biochemical and Molecular Nutrition Program, Friedman School of Nutrition Science and Policy Tufts University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lee","sequence":"additional","affiliation":[{"name":"Jean Mayer USDA Human Nutrition Research Center On Aging at Tufts University Boston Massachusetts USA"},{"name":"Tufts Graduate School of Biomedical Sciences Tufts University  Boston Massachusetts USA"},{"name":"Tufts University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirupa R.","family":"Matthan","sequence":"additional","affiliation":[{"name":"Jean Mayer USDA Human Nutrition Research Center On Aging at Tufts University Boston Massachusetts USA"},{"name":"Biochemical and Molecular Nutrition Program, Friedman School of Nutrition Science and Policy Tufts University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Lamon\u2010Fava","sequence":"additional","affiliation":[{"name":"Jean Mayer USDA Human Nutrition Research Center On Aging at Tufts University Boston Massachusetts USA"},{"name":"Biochemical and Molecular Nutrition Program, Friedman School of Nutrition Science and Policy Tufts University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang\u2010Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Jean Mayer USDA Human Nutrition Research Center On Aging at Tufts University Boston Massachusetts USA"},{"name":"Biochemical and Molecular Nutrition Program, Friedman School of Nutrition Science and Policy Tufts University  Boston Massachusetts USA"},{"name":"Tufts University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986\u2010023\u201000748\u2010x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13051442"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.13771"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-018-1711-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2019.158597"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24689"},{"key":"e_1_2_9_9_1","first-page":"198","article-title":"Effect of Tomato Extract Supplementation Against High\u2010Fat Diet\u2010Induced Hepatic Lesions","volume":"2","author":"Melendez\u2010Martinez A. J.","year":"2013","journal-title":"Hepatobiliary Surgery and Nutrition"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.114.200238"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201601083"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11051177"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9010141"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.110.000075"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cofs.2021.04.013"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djg081"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2015.01.004"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394\u2010007\u20100687\u20102"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12970-021-00415-7"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2015.01.003"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/135.5.1226"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101\u2010018\u20109597\u20106"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods13182882"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/cdn\/nzac049.009"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.115.220525"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.177.4.1"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549\u2010006\u20109405\u20107"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751\u20101097.1983.tb04509.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13530-020-00035-9"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13080931"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2023.1221013"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2020.158653"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020644"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxz106"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.113.181461"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-18-0188"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201700738"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqaa254"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.08.004"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2018.07.007"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2021.108862"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep16774"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.113.189613"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07\u20109574LSF"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2018.10.139"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/153537020222701002"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2012.10.067"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512095200"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2010.11.005"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2019.125232"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201800703"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-14-0154"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/68.6.1187"},{"key":"e_1_2_9_54_1","unstructured":"U.S. Department of Agriculture Agricultural Research Service FoodData Central (2019)."},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfca.2011.07.005"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2012-1147"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.6.1746"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201100387"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmy025"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.111.140756"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13216"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.199422"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202200580"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010nutr\u2010082117\u2010051841"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.111.150052"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-13-0178"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23696"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2026.117989"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u2010313X.2004.02263.x"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.25135\/rnp.150.19.07.1321"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/ffj.3256"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.117669"},{"key":"e_1_2_9_73_1","first-page":"878","article-title":"The Role of Hepatic SIRT1: From Metabolic Regulation to Immune Modulation and Multi\u2010Target Therapeutic Strategies","volume":"13","author":"Zhang H.","year":"2025","journal-title":"Journal of Clinical and Translational Hepatology"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2013.12.001"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2022.12922"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.970292"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3372"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.08.013"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010025\u201001089\u20101"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advnut.2022.10.007"}],"container-title":["Molecular Nutrition &amp; Food Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.70596","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mnfr.70596","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.70596","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:35:18Z","timestamp":1787895318000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mnfr.70596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":79,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/mnfr.70596"],"URL":"https:\/\/doi.org\/10.1002\/mnfr.70596","archive":["Portico"],"relation":{},"ISSN":["1613-4125","1613-4133"],"issn-type":[{"value":"1613-4125","type":"print"},{"value":"1613-4133","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70596"}}