{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:20:34Z","timestamp":1781115634233,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"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":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cannabinoid receptor type\u20101 (CB1) signaling plays an important part in maintenance of energy homeostasis, and CB1 blockers have shown promise in the treatment of obesity\u2010related metabolic dysfunction. Coffee peel contains abundant phytochemicals and possesses hypolipidemic and anti\u2010inflammatory activities. The present study aimed to elucidate the preventive effect of coffee peel polyphenols (CPPs) on nonalcoholic fatty liver disease (NAFLD) from the perspective of CB1 signaling. Male C57BL\/6J mice were fed a high\u2010fat and high\u2010cholesterol diet and CPPs (200\/400\u2009mg\/kg\/day) for 8\u2009weeks. Serum biochemical indexes and liver pathological analysis were used to evaluate the effect of CPPs on NAFLD. Untargeted\/targeted lipidomics analyses were used to evaluate the levels of endocannabinoid ligands and ceramides in serum and liver. The expression levels of proteins were detected by using Western blotting analysis. Administration of CPPs significantly improved hepatic steatosis, insulin resistance and biomarkers of liver function. Meanwhile, CPPs administration indicated reductions in endocannabinoid ligands, including anandamide and 2\u2010arachidonoylglycerol levels, associated with blockade of CB1 overexpression. Blockage of CB1 signaling depleted hepatic C16:0\u2010 and C18:0\u2010ceramide concentrations by enhancing ceramide metabolism. The reductions in hepatic ceramide concentrations contributed to down\u2010regulating sterol regulatory element\u2010binding protein\u20101c and up\u2010regulating proliferator activated receptor alpha, leading to decrease de novo lipogenesis and increase fatty acid \u03b2\u2010oxidation in the liver, respectively. This study demonstrated a novel mechanism that CPPs could ameliorate NAFLD through modulating CB1\u2010ceramide axis.<\/jats:p>","DOI":"10.1002\/ptr.8078","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T02:13:11Z","timestamp":1743214391000},"page":"2312-2323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Coffee peel polyphenols ameliorate nonalcoholic fatty liver disease by modulating cannabinoid receptor type\u20101\u2010ceramide axis"],"prefix":"10.1002","volume":"39","author":[{"given":"Ze\u2010kai","family":"Fan","sequence":"first","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao China"},{"name":"College of Food Science and Engineering Ocean University of China  Qingdao China"},{"name":"School of Public Health Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao China"},{"name":"School of Public Health Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010wei","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao China"},{"name":"School of Public Health Qingdao University  Qingdao 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 China"},{"name":"School of Public Health Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Nutrition &amp; Health Qingdao University  Qingdao China"},{"name":"School of Public Health Qingdao University  Qingdao China"},{"name":"Department of Food Science and Nutrition Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00406-0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/1319-3767.114505"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2020-001860"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1262-3636(08)74600-7"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29890"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6406"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2020.128169"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2020.109497"},{"issue":"11","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.3390\/medicina56110573","article-title":"Effects of the CB1 receptor antagonists AM6545 and AM4113 on insulin resistance in a high\u2010fructose high\u2010salt rat model of metabolic syndrome","volume":"56","author":"Eid B. 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