{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:29:31Z","timestamp":1791340171350,"version":"4.3.1"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Science and ICT","award":["NRF-2020R1A2C2005793"],"award-info":[{"award-number":["NRF-2020R1A2C2005793"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Hyperlipidemia, a syndrome characterized by an abnormal elevation of blood lipids, causes chronic lethal metabolic disorders. Although statins are regularly prescribed to patients, an alternative to treat the burden of excessive lipids is required for cholesterol control. In this study, it was found that the treatment of casein hydrolyzed by pepsin and trypsin induced trans-intestinal cholesterol excretion (TICE) through ATP-binding cassette subfamily G members 5 (ABCG5) expression. Next, we analyzed sequences of the peptides responsible for TICE induction, synthesized artificial peptides based on the sequences, and the hypolipidemic effects of the peptide treatments were assessed in both in vitro and in vivo models. We determined that two bioactive peptides contained in casein hydrolysates (SQSKVLPVPQK and HPHPHLSF) induced TICE through the expression of ABCG5 in enterocytes and suppressed hepatic mRNA expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1by ileal FGF19 expression both in an liver X receptor \u03b1 (LXR\u03b1)-mediated manner. In the hyperlipidemic mouse models, the oral administration of peptides reduced serum cholesterol levels through elevation of the ABCG5 expression in proximal intestine and fecal cholesterol secretion. Besides this, peptides induced ileal expression of fibroblast growth factor 15\/19 (FGF15\/19) and inhibited hepatic bile acid synthesis. We found that the oral treatment of casein-derived bioactive peptides could improve hyperlipidemia by regulating intestinal excretion and hepatic synthesis of cholesterols.<\/jats:p>","DOI":"10.3390\/nu12103058","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T10:46:17Z","timestamp":1601981177000},"page":"3058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Hypolipidemic Roles of Casein-Derived Peptides by Regulation of Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis"],"prefix":"10.3390","volume":"12","author":[{"given":"Sungmin","family":"Lee","sequence":"first","affiliation":[{"name":"Nuclear Science Research Institute, Pusan National University, Busan 46241, Korea"},{"name":"Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"BuHyun","family":"Youn","sequence":"additional","affiliation":[{"name":"Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea"},{"name":"Department of Biological Sciences, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17093","DOI":"10.1038\/nrdp.2017.93","article-title":"Familial hypercholesterolaemia","volume":"3","author":"Defesche","year":"2017","journal-title":"Nat. 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