Increased adipogenesis and altered adipocyte function contribute to the development of obesity and associated comorbidities. Fructose modified adipocyte metabolism compared to glucose, but the regulatory mechanisms and consequences for obesity are unknown. Genome-wide methylation and global transcriptomics in SGBS pre-adipocytes exposed to 0, 2.5, 5, and 10 mM fructose, added to a 5-mM glucose-containing medium, were analyzed at 0, 24, 48, 96, 192, and 384 h following the induction of adipogenesis. Time-dependent changes in DNA methylation compared to baseline (0 h) occurred during the final maturation of adipocytes, between 192 and 384 h. Larger percentages (0.1% at 192 h, 3.2% at 384 h) of differentially methylated regions (DMRs) were found in adipocytes differentiated in the glucose-containing control media compared to adipocytes differentiated in fructose-supplemented media (0.0006% for 10 mM, 0.001% for 5 mM, and 0.005% for 2.5 mM at 384 h). A total of 1437 DMRs were identified in 5237 differentially expressed genes at 384 h post-induction in glucose-containing (5 mM) control media. The majority of them inversely correlated with the gene expression, but 666 regions were positively correlated to the gene expression. Our studies demonstrate that DNA methylation regulates or marks the transformation of morphologically differentiating adipocytes (seen at 192 h), to the more mature and metabolically robust adipocytes (as seen at 384 h) in a genome-wide manner. Lower (2.5 mM) concentrations of fructose have the most robust effects on methylation compared to higher concentrations (5 and 10 mM), suggesting that fructose may be playing a signaling/regulatory role at lower concentrations of fructose and as a substrate at higher concentrations.

中文翻译：

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人类脂肪形成过程中的DNA甲基化和果糖的影响

脂肪生成的增加和脂肪细胞功能的改变有助于肥胖症和相关合并症的发展。与葡萄糖相比，果糖修饰脂肪细胞的代谢，但肥胖的调节机制和后果尚不清楚。分别在0、24、48、96、192和192℃下分析暴露于0、2.5、5和10 mM果糖的SGBS前脂肪细胞的全基因组甲基化和全局转录组学，并添加到含5mM葡萄糖的培养基中。诱导脂肪形成后384小时。与基线（0小时）相比，DNA甲基化的时间依赖性变化发生在脂肪细胞的最终成熟过程中，介于192和384小时之间。较大的百分比（192小时时为0.1％，3。在含葡萄糖的对照培养基中分化的脂肪细胞中，与在补充果糖的培养基中分化的脂肪细胞（10％的0.0006％，5 mM的0.001％和0.005％）相比，在384小时发现2％的甲基化差异区域（DMR）。在384 h时为2.5 mM）。在含葡萄糖（5 mM）的对照培养基中诱导后384小时，在5237个差异表达的基因中共鉴定出1437个DMR。它们中的大多数与基因表达成反相关，但是666个区域与基因表达成正相关。我们的研究表明，DNA甲基化以全基因组的方式调节或标志着形态分化的脂肪细胞（在192 h处可见）向更成熟和代谢功能强大的脂肪细胞（在384 h处可见）的转化。降低（2。