1 The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet2 Section for Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet3 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.4 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden5 Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Sweden6 Section for Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
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/m2) underwent a 14-day VLCD followed by RYGB. Nonobese patients (n = 6, BMI 25.7± 2.1 kg/m2) 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.
Surgery for Obesity and Related Diseases, 2014, Vol 10, Issue 4, p. 671-8