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

Henriette Kirchner; Carolina Nylen; Samantha Laber; Romain Barrès; Jie Yan; Anna Krook; Juleen R. Zierath; Erik Näslund

doi:10.1016/j.soard.2013.12.019

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

Henriette Kirchner, Carolina Nylen, Samantha Laber, Romain Barrès, Jie Yan, Anna Krook, Juleen R. Zierath, Erik Näslund^*

^*Corresponding author for this work

Department of Internal Medicine I

64 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Surgery for Obesity and Related Diseases
Volume	10
Issue number	4
Pages (from-to)	671-678
Number of pages	8
ISSN	1550-7289
DOIs	https://doi.org/10.1016/j.soard.2013.12.019
Publication status	Published - 01.01.2014

Funding

The authors thank Charlotte Ceruti at the Karolinska Institutet for her help with the sample preparation. This work was supported by The Strategic Diabetes Program at Karolinska Institutet, European Research Council Ideas Program (ICEBERG, ERC-2008-AdG23285), Swedish Research Council, Swedish Diabetes Association, Strategic Research Foundation, Knut and Alice Wallenberg Foundation, Novo Nordisk Foundation, and the Stockholm County Council supported this research. H.K. is supported by an EMBO long-term fellowship. The authors declare no conflicts of interest, financial or otherwise.

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10.1016/j.soard.2013.12.019

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@article{87ae4bd769764d11a66a0ddd19d432e0,

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

abstract = "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.",

author = "Henriette Kirchner and Carolina Nylen and Samantha Laber and Romain Barr{\`e}s and Jie Yan and Anna Krook and Zierath, \{Juleen R.\} and Erik N{\"a}slund",

year = "2014",

month = jan,

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doi = "10.1016/j.soard.2013.12.019",

language = "English",

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journal = "Surgery for Obesity and Related Diseases",

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TY - JOUR

T1 - Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en y gastric bypass

AU - Kirchner, Henriette

AU - Nylen, Carolina

AU - Laber, Samantha

AU - Barrès, Romain

AU - Yan, Jie

AU - Krook, Anna

AU - Zierath, Juleen R.

AU - Näslund, Erik

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84908088938

U2 - 10.1016/j.soard.2013.12.019

DO - 10.1016/j.soard.2013.12.019

M3 - Journal articles

C2 - 24837562

AN - SCOPUS:84908088938

SN - 1550-7289

VL - 10

SP - 671

EP - 678

JO - Surgery for Obesity and Related Diseases

JF - Surgery for Obesity and Related Diseases

IS - 4

ER -

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

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