Marie-Claude Vohl*, Frederic Guenard, Andre Tchernof, Yves Deshaies, Katherine Cianflone, John G. Kral, Picard Marceau
Context Biliopancreatic diversion with duodenal switch (BPD-DS), a metabolic bariatric operation, induces durable loss of excess weight and reduced cardiometabolic risk. Altered epigenetic marks are mechanistically associated with environment-driven phenotypic variations. Objective The current study aimed to compare gene methylation levels before and after BPD-DS to identify epigenetic marks potentially linked to metabolic improvements induced by BPD-DS. Design and patients Metabolic risk factors and gene methylation levels of 20 women studied mean 12 years (range 4-22) after BPD-DS were compared to those of 20 severely obese surgical candidates as controls, matched for pre-surgical age, body mass index and dyslipidemia and hypertension prevalences. Whole-genome blood DNA methylation analysis enabled between-group differential methylation analyses. We calculated correlations between methylation levels of the most differentially methylated CpG sites and plasma glucose and insulin levels and HOMA-IR. Results Differential methylation analysis identified 15,343 genes demonstrating at least one differentially methylated CpG site (p<1.43x10-7). Diabetic and inflammation/immune functions were among the most overrepresented from the 200 genes exhibiting the largest group differences in methylation levels. CpG sites methylation levels of genes related to insulin action correlated significantly with fasting insulin levels and homeostatic model of insulin resistance (p≤0.002 for all). Conclusion These findings suggest that differential methylation levels in obese controls versus treated women may partially explain the durable metabolic improvements after BPD-DS.
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