Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en y gastric bypass

Conclusion: RYGB induced more profound epigenetic changes than VLCD in promoters of the tested genes in whole blood. Changes in DNA methylation may contribute to the improved overall metabolic health after RYGB. (Surg Obes Relat Dis 2014:10:671 678.).

Background: Early benefits of Roux-en Y gastric bypass (RYGB) are partly mediated by the caloric restriction that patients undergo before and acutely after the procedure. Altered DNA methylation occurs in metabolic diseases including obesity, as well as in skeletal, muscle eight months after RYGB. The objective of this study was to test whether promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGCI A), pyruvate dehydrogenase kinase isozyme-4 (PDK4), transcription factor A (TFAM), interleukin-1 beta (IL] B), interleukin-6 (1L6) and tumor necrosis factor-a (TNF is altered in blood after a very low calorie diet (VLCD) or RYGB.

Methods: Obese nondiabetic patients (n = 18, body mass index LBMII 42.3 4.9 kg/rn2) underwent a 14-day VLCD followed by RYGB. Nonobese patients (n = 6, BMI 25.7 2.1 kg/rn2) undergoing elective cholecystectorny served as controls. DNA methylation of selected promoter regions was measured in whole blood before and after VLCD. A subgroup of seven patients was studied 1 2 days and 12 3 months after RYGB. Promoter methylation was measured using methylated DNA capture and quantitative real-time polymerase chain reaction (PCR).

Results: VLCD decreased promoter methylation of PPARGCI A. Methylation of PPARGCI A, TFAM, IL] B, 1L6, and TNF promoters was changed two days after RYGB. Similar changes were also seen on day one after cholecystectomy. Moreover, rnethylation increased in PDK4, IL] B, 1L6, and TNF promoters 12 months after RYGB.