Abstract
BackgroundIncreased 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.ResultsTime-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.ConclusionsOur 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.
Highlights
Increased adipogenesis and altered adipocyte function contribute to the development of obesity and associated comorbidities
Genome-wide DNA methylation and transcriptomic during adipocyte differentiation Genome-wide DNA methylation was measured using the Illumina 450K BeadChip at different time points compared to baseline during adipocyte differentiation
The integration of DNA methylation and transcriptomic data identified differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in genes which were differentially expressed during adipocyte differentiation
Summary
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. The most recent meta-analysis of 13 studies with a combined total of 49,591 participants and over 14,000 cases showed a linear association between fructose intake and metabolic syndrome (MetS). This adverse correlation was specific to sugar-sweetened beverages (SSB) [60] and not other fructose-containing foods (e.g., yogurt, whole fruits) indicating that the food matrix plays a significant (and expected) role in the metabolism of nutrients.
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