Henriette Kirchner1, Carolina Nylen1, Samantha Laber1, Romain Barrès2, Jie Yan1, Anna Krook3, Juleen R Zierath4, Erik Näslund5. 1. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 2. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. 3. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. 4. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. 5. Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Sweden. Electronic address: Erik.Naslund@ki.se.
Abstract
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.
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 nondiabeticpatients (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.
Authors: Michael L Multhaup; Marcus M Seldin; Andrew E Jaffe; Xia Lei; Henriette Kirchner; Prosenjit Mondal; Yuanyuan Li; Varenka Rodriguez; Alexander Drong; Mehboob Hussain; Cecilia Lindgren; Mark McCarthy; Erik Näslund; Juleen R Zierath; G William Wong; Andrew P Feinberg Journal: Cell Metab Date: 2015-01-06 Impact factor: 27.287
Authors: Carolina Ferreira Nicoletti; Carla Barbosa Nonino; Bruno Affonso Parenti de Oliveira; Marcela Augusta de Souza Pinhel; Maria Luisa Mansego; Fermin Ignacio Milagro; Maria Angeles Zulet; José Alfredo Martinez Journal: Obes Surg Date: 2016-03 Impact factor: 4.129
Authors: Mohamed M Ali; Dina Naquiallah; Maryam Qureshi; Mohammed Imaduddin Mirza; Chandra Hassan; Mario Masrur; Francesco M Bianco; Patrice Frederick; Giulianotti P Cristoforo; Antonio Gangemi; Shane A Phillips; Abeer M Mahmoud Journal: Epigenetics Date: 2021-01-25 Impact factor: 4.528