Integrative whole-genome methylation and transcriptome analysis reveals epigenetic modulation of glucose metabolism by dietary berberine in blunt snout bream (Megalobrama amblycephala)

IF 1.9 3区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology B-Biochemistry & Molecular Biology Pub Date : 2025-04-16 DOI:10.1016/j.cbpb.2025.111098

Xiaoyan Jia, Wei Qiang, Le Chang, Kang Xiao, Ronghua Zhou, Qiyong Qiu, Guangzhen Jiang, Xiangfei Li, Cheng Chi, Wenbin Liu, Dingdong Zhang

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Abstract

The present research was designed to explore the epigenetic mechanism by which dietary berberine (BBR) affects glucose metabolism in fish. Blunt snout bream (Megalobrama amblycephala) is susceptible to disturbances in glucose metabolism when subjected to prolonged high-carbohydrate diets. This study aimed to elucidate whether BBR can enhance glucose regulation in M. amblycephala via modulating DNA methylation levels. Fish (average weight of 20.36 ± 1.44 g) were administered a normal-carbohydrate diet (NC, 30 % carbohydrate), a high-carbohydrate diet (HC, 43 % carbohydrate), or a high-carbohydrate diet supplemented with 50 mg/kg berberine (HB) for 10 weeks. Subsequently, global DNA methylation level, whole-genome bisulfite sequencing (WGBS), RNA-seq, bisulfite sequencing PCR, and real-time quantitative PCR were employed to analyze the DNA methylation patterns and transcription results of the liver genome. The findings indicated that high carbohydrate diets induced glucose metabolism disorders in M. amblycephala, whereas BBR mitigated these metabolic disturbances by reducing methylation levels. WGBS results revealed that CG-type cytosine methylation predominated, and that DNA methylation mainly occurred in promoter, intron, and exon regions. Furthermore, analyses demonstrated a negative correlation between DNA methylation around the transcriptional start site and gene expression levels for 47 genes. Functional enrichment analysis revealed that these genes were associated with 60 KEGG pathways, including 12 genes implicated in the amelioration of insulin resistance, reduction of gluconeogenesis, and maintenance of glucose homeostasis. Consequently, we generated a comprehensive catalog of liver DNA methylation in M. amblycephala, which provides a foundational framework for future investigations into the epigenetic regulation of glucose metabolism by BBR.

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全基因组甲基化和转录组整合分析揭示钝口鳊鱼（Megalobrama amblycephala）膳食小檗碱对葡萄糖代谢的表观遗传调节作用

本研究旨在探讨饲料中小檗碱（BBR）影响鱼类葡萄糖代谢的表观遗传机制。钝口鲷（Megalobrama amblycephala）在长期高碳水化合物饮食时易受葡萄糖代谢紊乱的影响。本研究旨在阐明BBR是否可以通过调节DNA甲基化水平来增强双头m.s amblycephala的葡萄糖调节。鱼（平均体重20.36±1.44 g）被给予正常碳水化合物饮食（NC， 30%碳水化合物），高碳水化合物饮食（HC， 43%碳水化合物），或高碳水化合物饮食中添加50 mg/kg小檗碱（HB），为期10周。随后，采用全局DNA甲基化水平、全基因组亚硫酸氢盐测序（WGBS）、RNA-seq、亚硫酸氢盐测序PCR和实时定量PCR分析肝脏基因组DNA甲基化模式和转录结果。研究结果表明，高碳水化合物饮食会引起双头m.a blblycephala的糖代谢紊乱，而BBR通过降低甲基化水平来减轻这些代谢紊乱。WGBS结果显示cg型胞嘧啶甲基化占主导地位，DNA甲基化主要发生在启动子、内含子和外显子区域。此外，分析表明47个基因转录起始位点附近的DNA甲基化与基因表达水平呈负相关。功能富集分析显示，这些基因与60个KEGG通路相关，其中12个基因与改善胰岛素抵抗、减少糖异生和维持葡萄糖稳态有关。因此，我们生成了一个全面的双头m.b amblycephala肝脏DNA甲基化目录，这为未来研究BBR对葡萄糖代谢的表观遗传调控提供了基础框架。

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来源期刊

Comparative Biochemistry and Physiology B-Biochemistry & Molecular Biology 生物-动物学

CiteScore

4.60

自引率

4.50%

发文量

审稿时长

22 days

期刊介绍： Comparative Biochemistry & Physiology (CBP) publishes papers in comparative, environmental and evolutionary physiology. Part B: Biochemical and Molecular Biology (CBPB), focuses on biochemical physiology, primarily bioenergetics/energy metabolism, cell biology, cellular stress responses, enzymology, intermediary metabolism, macromolecular structure and function, gene regulation, evolutionary genetics. Most studies focus on biochemical or molecular analyses that have clear ramifications for physiological processes.