{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:20:33Z","timestamp":1790659233589,"version":"4.1.0"},"reference-count":23,"publisher":"Brieflands","issue":"1","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["brieflands.com"],"crossmark-restriction":false},"short-container-title":["Iran J Pharm Res"],"abstract":"<jats:p>Background: High-fat diet (HFD)-driven hepatic steatosis is associated with impaired mitochondrial fatty acid oxidation and dysregulated expression of genes that control lipid disposal. Carnitine palmitoyltransferase 1\u03b1 (CPT1\u03b1), encoded by Cpt1a, is the rate-limiting enzyme for mitochondrial fatty acid \u03b2-oxidation and responds to nutritional stress. However, the chromatin mechanisms that regulate Cpt1a in diet-induced steatosis remain incompletely defined. Objectives: To map histone modifications at the hepatic Cpt1a locus and determine whether berberine (BBR) is associated with the restoration of Cpt1a transcription through histone acetylation remodeling. Methods: Male Sprague-Dawley rats were assigned to the normal diet (ND), high-fat diet (HFD), or berberine (BBR)+HFD group (n = 8 initially), with individual rats as the experimental unit. ChIP-qPCR was performed on archived liver samples (ND, n = 6; HFD, n = 8; BBR+HFD, n = 8) and normalized to input DNA. In BRL cells, TSA (100 nM) and SAHA (20 \u03bcM) were used to assess HDAC-sensitive regulation of Cpt1a. Results: HFD reduced H3\/H4 acetylation and increased H3K9 methylation at Cpt1a regulatory regions. BBR restored H3\/H4 acetylation, selectively reduced H3K9me3 at +12 kb, and attenuated HFD-induced increases in HDAC2 and SIRT2 mRNA (approximately 40-fold and 3.8-fold, respectively) toward baseline. TSA and SAHA increased Cpt1a mRNA at 24 h by approximately 8.1-fold and 5.4-fold, respectively. Palmitate reduced Cpt1a expression by approximately 58%, and this repression was reversed by BBR or TSA. Conclusions: BBR alleviates HFD-induced hepatic steatosis, concomitant with the restoration of Cpt1a histone acetylation and modulation of HDAC2\/SIRT2. These data support, but do not prove, an HDAC2\/SIRT2-linked chromatin mechanism and should be interpreted as a candidate pathway requiring further functional validation.<\/jats:p>","DOI":"10.5812\/ijpr-170783","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T08:21:16Z","timestamp":1783498876000},"update-policy":"https:\/\/doi.org\/10.5812\/crossmark_update_policy","source":"Crossref","is-referenced-by-count":1,"title":["Berberine Alleviates Hepatic Steatosis by Restoring CPT1\u03b1 Histone Acetylation and Modulating HDAC2\/SIRT2"],"prefix":"10.5812","volume":"25","author":[{"given":"Chenye","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huandong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxia","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3819","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"key-A170783REF1-1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.04.031"},{"key":"key-A170783REF2-2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.11.034"},{"key":"key-A170783REF3-3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0104-9"},{"key":"key-A170783REF4-4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23719"},{"key":"key-A170783REF5-5","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqz046"},{"key":"key-A170783REF6-6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2018.12.009"},{"key":"key-A170783REF7-7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2019.10.005"},{"key":"key-A170783REF8-8","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-015-0383-6"},{"key":"key-A170783REF9-9","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14079"},{"key":"key-A170783REF10-10","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M001958"},{"key":"key-A170783REF11-11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134172"},{"key":"key-A170783REF12-12","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2015.02.021"},{"key":"key-A170783REF13-13","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.20.3.351"},{"key":"key-A170783REF14-14","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24140"},{"key":"key-A170783REF15-15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.10.008"},{"key":"key-A170783REF16-16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.10.134"},{"key":"key-A170783REF17-17","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1000-6"},{"key":"key-A170783REF18-18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv161"},{"key":"key-A170783REF19-19","doi-asserted-by":"publisher","DOI":"10.1016\/j.tplants.2015.07.005"},{"key":"key-A170783REF20-20","doi-asserted-by":"publisher","DOI":"10.1007\/1-4020-5466-1_15"},{"key":"key-A170783REF21-21","doi-asserted-by":"publisher","DOI":"10.1038\/nm1135"},{"key":"key-A170783REF22-22","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2021.4964"},{"key":"key-A170783REF23-23","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700602R"}],"container-title":["Iranian Journal of Pharmaceutical Research"],"original-title":[],"link":[{"URL":"https:\/\/brieflands.com\/journals\/ijpr\/articles\/170783","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/brieflands.com\/journals\/ijpr\/articles\/170783","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T08:21:16Z","timestamp":1783498876000},"score":1,"resource":{"primary":{"URL":"https:\/\/brieflands.com\/journals\/ijpr\/articles\/170783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,6,2]]}},"alternative-id":["375de268fdecf6f01496035919fda49662641a13"],"URL":"https:\/\/doi.org\/10.5812\/ijpr-170783","relation":{},"ISSN":["1726-6890"],"issn-type":[{"value":"1726-6890","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]}}}