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

Surg Obes Relat Dis. 2014 Jul-Aug;10(4):671-8. doi: 10.1016/j.soard.2013.12.019. Epub 2014 Jan 28.


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 (PPARGC1 A), pyruvate dehydrogenase kinase isozyme-4 (PDK4), transcription factor A (TFAM), interleukin-1 beta (IL1 B), interleukin-6 (IL6) and tumor necrosis factor-α (TNF) is altered in blood after a very low calorie diet (VLCD) or RYGB.

Methods: Obese nondiabetic patients (n = 18, body mass index [BMI] 42.3 ± 4.9 kg/m(2)) underwent a 14-day VLCD followed by RYGB. Nonobese patients (n = 6, BMI 25.7 ± 2.1 kg/m(2)) undergoing elective cholecystectomy 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 PPARGC1 A. Methylation of PPARGC1 A, TFAM, IL1 B, IL6, and TNF promoters was changed two days after RYGB. Similar changes were also seen on day one after cholecystectomy. Moreover, methylation increased in PDK4, IL1 B, IL6, and TNF promoters 12 months after RYGB.

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.

Keywords: Blood; DNA methylation; Gastric bypass; Very low calorie diet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Caloric Restriction*
  • Case-Control Studies
  • DNA Methylation*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gastric Bypass*
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Obesity, Morbid / genetics
  • Obesity, Morbid / metabolism*
  • Obesity, Morbid / therapy*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Promoter Regions, Genetic*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • DNA-Binding Proteins
  • Interleukin-1beta
  • Interleukin-6
  • Mitochondrial Proteins
  • PDK4 protein, human
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • TFAM protein, human
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Protein Serine-Threonine Kinases