Berberine Alleviates Hepatic Steatosis by Restoring CPT1α Histone Acetylation and Modulating HDAC2/SIRT2
| Author | Chenye Shi | en |
| Author | Shuai Ma | en |
| Author | Hua Bian | en |
| Author | Qiong Liu | en |
| Author | Huandong Lin | en |
| Author | Xin Gao | en |
| Author | Haifu Wu | en |
| Author | Hongmei Yan | en |
| Author | Xinxia Chang | en |
| Issued Date | 2026-12-31 | en |
| Abstract | 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 1α (CPT1α), encoded by Cpt1a, is the rate-limiting enzyme for mitochondrial fatty acid β-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 μM) 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. | en |
| DOI | https://doi.org/10.5812/ijpr-170783 | en |
| URI | https://brieflands.com/journals/ijpr/articles/170783 | en |
| Keyword | Berberine (BBR) | en |
| Keyword | Carnitine Palmitoyltransferase 1α | en |
| Keyword | Histone Modifications | en |
| Keyword | Hepatic Steatosis | en |
| Publisher | Brieflands | en |
| Title | Berberine Alleviates Hepatic Steatosis by Restoring CPT1α Histone Acetylation and Modulating HDAC2/SIRT2 | en |
| Type | Research Article | en |
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