High-fructose corn syrup intake has stronger effects on the transcription level of hepatic lipid metabolism-related genes, via DNA methylation modification, in childhood and adolescence than in other generations
High-fructose corn syrup intake has stronger effects on the transcription level of hepatic lipid metabolism-related genes, via DNA methylation modification, in childhood and adolescence than in other generations
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DOI：
10.1016/j.lfs.2022.120638
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发表时间：
2022-05-19
期刊：
影响因子：
6.1
通讯作者：
Ohashi, Koji
中科院分区：
文献类型：
--
作者：
Mizuno, Genki;Yamada, Hiroya;Ohashi, Koji
目的：本研究旨在通过高果糖玉米糖浆（HFCS）摄入实验大鼠模型，通过DNA甲基化分析不同年龄大鼠肝脏脂质代谢敏感性的差异。主要方法：实验分为三个时期：儿童和青春期（出生后（PD）21-60天），青年期（PD 61 -100）和成年期（PD 101 -140）。不同年龄组的大鼠被分配接受水（C：对照组）或20%HFCS溶液（H：HFCS喂养组）。我们使用实时PCR测定了肝脏过氧化物酶体增殖物激活受体α（Ppara）、肉毒碱棕榈酰转移酶1A（Cpt 1a）、脂肪酸合成酶（Fasn）和过氧化物酶体增殖物激活受体-γ共激活因子1 α（Pgc 1a）的mRNA水平。此外，我们使用焦磷酸测序法检测了Ppara、Cpt 1a、Fasn和Pgc 1a的DNA甲基化水平。关键发现：儿童和青少年期Cpt 1a和Ppara的基因表达在H组中显著低于C组。相反，H组中Fasn和Pgc 1a的表达显著高于C组。此外，在儿童期和青少年期的H组中存在Cpt 1a和Ppara的高甲基化和Fasn和Pgc 1a的低甲基化。然而，在青年组和成年组中仅观察到一种基因表达和甲基化变化。我们发现，HFCS摄入大鼠在儿童期和青春期比其他世代具有更强的脂质代谢效应，其机制涉及表观遗传调控。意义：我们期望这些研究结果将是未来阐明生长阶段不同影响的突破。
Aims: This study aimed to analyze differences in sensitivity to hepatic lipid metabolism at different ages, through DNA methylation, using an experimental rat model of high-fructose corn syrup (HFCS) intake. Main methods: The experimental was divided into three periods: childhood and adolescence (postnatal day (PD) 21-60), young adulthood (PD61-100), and adulthood (PD101-140). Rats in the different age groups were assigned to receive either water (C: control group) or 20% HFCS solution (H: HFCS-fed group). We measured hepatic mRNA levels of peroxisome proliferator-activated receptor alpha (Ppara), carnitine palmitoyltransferase 1A (Cpt1a), fatty acid synthase (Fasn), and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (Pgc1a) using real-time PCR. Additionally, we examined the DNA methylation levels of Ppara, Cpt1a, Fasn, and Pgc1a using pyrosequencing. Key findings: Gene expressions of Cpt1a and Ppara in childhood and adolescence were significantly lower in the H group than in the C group. Conversely, Fasn and Pgc1a expressions were significantly higher in the H group than in the C group. Additionally, there was hypermethylation of Cpt1a and Ppara and hypomethylation of Fasn and Pgc1a in the H groups of childhood and adolescence. However, only one gene expression and methylation change was observed in young adulthood and adulthood groups. We found that HFCS intake in rats had stronger lipid metabolic effects in childhood and adolescence than in other generations, and that its mechanism involved epigenetic regulation. Significance: We anticipate that these research findings will be a breakthrough for elucidating the varying effects of growth stage in the future.