Weight loss after Roux-En-Y gastric bypass surgery reveals skeletal muscle DNA methylation changes
| Autor: | Tonya R. Benjamin, James A. Madura, Dawn K. Coletta, Luis A. Garcia, Samantha E. Day, Richard L. Coletta, Lori R. Roust, Lawrence J. Mandarino, Eleanna De Filippis, Baltazar Campos |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Beta-3 adrenergic receptor medicine.medical_specialty Vastus lateralis muscle Gastric Bypass Skeletal muscle 030209 endocrinology & metabolism Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Weight loss Next generation sequencing Internal medicine Weight Loss Genetics medicine Humans Obesity Epigenetics Muscle Skeletal Molecular Biology Genetics (clinical) Bariatric surgery DNA methylation business.industry Research Methylation Middle Aged 030104 developmental biology medicine.anatomical_structure Endocrinology Reduced representation bisulfite sequencing Female medicine.symptom business Developmental Biology |
| Zdroj: | Clinical Epigenetics |
| ISSN: | 1868-7083 1868-7075 |
| Popis: | Background The mechanisms of weight loss and metabolic improvements following bariatric surgery in skeletal muscle are not well known; however, epigenetic modifications are likely to contribute. The aim of our study was to investigate skeletal muscle DNA methylation after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Muscle biopsies were obtained basally from seven insulin-resistant obese (BMI > 40 kg/m2) female subjects (45.1 ± 3.6 years) pre- and 3-month post-surgery with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. Four lean (BMI 2) females (38.5 ± 5.8 years) served as controls. We performed reduced representation bisulfite sequencing next generation methylation on DNA isolated from the vastus lateralis muscle biopsies. Results Global methylation was significantly higher in the pre- (32.97 ± 0.02%) and post-surgery (33.31 ± 0.02%) compared to the lean (30.46 ± 0.02%), P versus pre-surgery (Benjamini–Hochberg q versus the lean controls (Benjamini–Hochberg q versus the lean controls, 2885 DMCs were altered (Benjamini–Hochberg q ITGB3) promoter and KIAA0284 exon, respectively. ITGB3 methylation was significantly decreased in the post-surgery (0.5 ± 0.5%) and lean controls (0 ± 0%) versus pre-surgery (13.6 ± 2.7%, P ITGB3 gene expression (fold change + 1.52, P = 0.0087). In addition, we showed that ITGB3 promoter methylation in vitro significantly suppressed transcriptional activity (P ITGB3 chr17.45,330,989 identified three putative transcription factor binding motifs; PAX-5, p53 and AP-2alphaA. Conclusions These results demonstrate that weight loss after RYGB alters the epigenome through DNA methylation. In particular, this study highlights ITGB3 as a novel gene that may contribute to the metabolic improvements observed post-surgery. Future additional studies are warranted to address the exact mechanism of ITGB3 in skeletal muscle. |
| Databáze: | OpenAIRE |
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