{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:34:23Z","timestamp":1782282863044,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T00:00:00Z","timestamp":1709337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073538"],"award-info":[{"award-number":["82073538"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Endocannabinoid signaling regulates energy homeostasis, and is tightly associated with nonalcoholic fatty liver disease (NAFLD). The study previously finds that supplementation of docosahexaenoic acid (DHA) has superior function to ameliorate NAFLD compared with eicosapentaenoic acid (EPA), however, the underlying mechanism remains elusive. The present study aims to investigate whether DHA intervention alleviates NAFLD via endocannabinoid system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>In a case\u2013control study, the serum endocannabinoid ligands in 60 NAFLD and 60 healthy subjects are measured. Meanwhile, NAFLD model is established in mice fed a high\u2010fat and \u2010cholesterol diet (HFD) for 9 weeks. DHA or EPA is administrated for additional 9 weeks. Serum primary endocannabinoid ligands, namely anandamide (AEA) and 2\u2010arachidoniylglycerol (2\u2010AG), are significantly higher in individuals with NAFLD compared with healthy controls. NAFLD model shows that serum 2\u2010AG concentrations and adipocyte cannabinoid receptor 1 expression levels are significantly lower in DHA group compared with HFD group. Lipidomic and targeted ceramide analyses further confirm that endocannabinoid signaling inhibition has exerted deletion of hepatic C16:0\u2010ceramide contents, resulting in down\u2010regulation of de novo fatty acid synthesis and up\u2010regulation of fatty acid \u03b2\u2010oxidation related protein expression levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This work elucidates that DHA has improved NAFLD by suppressing endocannabinoid system.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202300616","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T13:04:42Z","timestamp":1709384682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Docosahexaenoic Acid Modulates Nonalcoholic Fatty Liver Disease by Suppressing Endocannabinoid System"],"prefix":"10.1002","volume":"68","author":[{"given":"Yan\u2010fang","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao 266071 China"},{"name":"School of Public Health Qingdao University  Qingdao 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze\u2010kai","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao 266071 China"},{"name":"School of Public Health Qingdao University  Qingdao 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin\u2010peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao 266071 China"},{"name":"School of Public Health Qingdao University  Qingdao 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao 266071 China"},{"name":"School of Public Health Qingdao University  Qingdao 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0116-8609","authenticated-orcid":false,"given":"Xiao\u2010fei","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao 266071 China"},{"name":"School of Public Health Qingdao University  Qingdao 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao 266071 China"},{"name":"Qingdao University Function Center of Medical Nutrition  Qingdao 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(21)00020-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17050774"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101274"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(97)80287-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-052220-021800"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.09.020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2018.01.009"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2019.154028"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20100008"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)01343-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.03.001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2679"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-90219-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-999-0481-6"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12673"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.03.001"},{"key":"e_1_2_9_18_1","first-page":"1506","volume":"5","author":"Watkins B. 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