Weight loss after Roux-En-Y gastric bypass surgery reveals skeletal muscle DNA methylation changes

Garcı́a, Luis; Day, Samantha E.; Coletta, Richard L.; Campos, Baltazar; Benjamin, Tonya R.; Filippis, Eleanna De; Madura, James A.; Mandarino, Lawrence J.; Roust, Lori R.; Coletta, Dawn K.

doi:10.1186/s13148-021-01086-6

Cited by 10 publications

(10 citation statements)

References 46 publications

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“…We hypothesized that averaged global methylation pre- versus post-training would be unchanged following the training. We [ 19 ] and others [ 20 ] have performed methylation studies with and without various interventions and showed minimal to no changes at the global level. We showed a similar finding here in the present study.…”

Section: Discussionmentioning

confidence: 99%

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Can Exercise Training Alter Human Skeletal Muscle DNA Methylation?

et al. 2022

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Skeletal muscle is highly plastic and dynamically regulated by the body’s physical demands. This study aimed to determine the plasticity of skeletal muscle DNA methylation in response to 8 weeks of supervised exercise training in volunteers with a range of insulin sensitivities. We studied 13 sedentary participants and performed euglycemic hyperinsulinemic clamps with basal vastus lateralis muscle biopsies and peak aerobic activity (VO2 peak) tests before and after training. We extracted DNA from the muscle biopsies and performed global methylation using Illumina’s Methylation EPIC 850K BeadChip. Training significantly increased peak aerobic capacity and insulin-stimulated glucose disposal. Fasting serum insulin and insulin levels during the steady state of the clamp were significantly lower post-training. Insulin clearance rates during the clamp increased following the training. We identified 13 increased and 90 decreased differentially methylated cytosines (DMCs) in response to 8 weeks of training. Of the 13 increased DMCs, 2 were within the following genes, FSTL3, and RP11-624M8.1. Of the 90 decreased DMCs, 9 were within the genes CNGA1, FCGR2A, KIF21A, MEIS1, NT5DC1, OR4D1, PRPF4B, SLC26A7, and ZNF280C. Moreover, pathway analysis showed an enrichment in metabolic and actin-cytoskeleton pathways for the decreased DMCs, and for the increased DMCs, an enrichment in signal-dependent regulation of myogenesis, NOTCH2 activation and transmission, and SMAD2/3: SMAD4 transcriptional activity pathways. Our findings showed that 8 weeks of exercise training alters skeletal muscle DNA methylation of specific genes and pathways in people with varying degrees of insulin sensitivity.

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Section: Discussionmentioning

confidence: 99%

“…Participants reported fasting to either the CSIU or CATS to undergo an 80 mU/m 2 euglycemic hyperinsulinemic clamp with muscle biopsy, as previously described [ 19 , 39 ]. Briefly, a primed infusion of 6,6 di-deuterated glucose was started at −120 min to determine the basal rate of glucose metabolism.…”

Section: Methodsmentioning

confidence: 99%

Can Exercise Training Alter Human Skeletal Muscle DNA Methylation?

et al. 2022

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“…Some authors have also observed lower overall methylation levels after RYGB in subcutaneous adipose tissue (SAT) [ 16 , 17 ]. Conversely, more recent studies have observed higher methylation levels at cytosine-phosphate-guanine dinucleotides, or CpG sites, after RYGB and SG procedures in peripheral blood [ 15 ], as well as higher global methylation levels in skeletal muscle after RYGB [ 18 ]. These discrepancies may partly be explained by tissue-specific DNA methylation [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular remodeling of adipose tissue is associated with metabolic recovery after weight loss surgery

et al. 2022

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Background Bariatric surgery is an effective therapy for individuals with severe obesity to achieve sustainable weight loss and to reduce comorbidities. Examining the molecular signature of subcutaneous adipose tissue (SAT) following different types of bariatric surgery may help in gaining further insight into their distinct metabolic impact. Results Subjects undergoing biliopancreatic diversion with duodenal switch (BPD-DS) showed a significantly higher percentage of total weight loss than those undergoing gastric bypass or sleeve gastrectomy (RYGB + SG) (41.7 ± 4.6 vs 28.2 ± 6.8%; p = 0.00005). Individuals losing more weight were also significantly more prone to achieve both type 2 diabetes and dyslipidemia remission (OR = 0.75; 95%CI = 0.51–0.91; p = 0.03). Whole transcriptome and methylome profiling showed that bariatric surgery induced a profound molecular remodeling of SAT at 12 months postoperative, mainly through gene down-regulation and hypermethylation. The extent of changes observed was greater following BPD-DS, with 61.1% and 49.8% of up- and down-regulated genes, as well as 85.7% and 70.4% of hyper- and hypomethylated genes being exclusive to this procedure, and mostly associated with a marked decrease of immune and inflammatory responses. Weight loss was strongly associated with genes being simultaneously differentially expressed and methylated in BPD-DS, with the strongest association being observed for GPD1L (r2 = 0.83; p = 1.4 × 10–6). Conclusions Present findings point to the greater SAT molecular remodeling following BPD-DS as potentially linked with higher metabolic remission rates. These results will contribute to a better understanding of the metabolic pathways involved in the response to bariatric surgery and will eventually lead to the development of gene targets for the treatment of obesity. Trial registration ClinicalTrials.gov NCT02390973.

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“…It was observed a DNA methylation remodeling in adipose tissue after 6 months postoperative, in accordance with previous reports of changes in blood, liver, muscle, and adipose tissue. [ 14–17 ] It has been shown that the methylation profiles of subcutaneous adipose tissue have a high correlation with visceral adipose tissue, so this tissue could be a good mirror of what occurs in other fat deposits. [ 12 ]…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Remodeling after Bariatric Surgery Correlates with Clinical Parameters

et al. 2023

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The altered functions of adipose tissue are one of the main issues in obesity. Bariatric surgery is associated with improvement of obesity associated comorbidities. Here DNA methylation remodeling in adipose tissue after bariatric surgery is examined. After six months postoperative, DNA methylation shows changes in 1155 CpG sites, 66 of these sites correlate with body mass index. Some sites also show correlation with LDL‐C, HDL‐C, total cholesterol, and triglycerides. CpG sites are located in genes that have not previously been linked to obesity or metabolic diseases. GNAS complex locus is one of those that presented CpG site with the greatest changes after surgery, and the most significant correlation with BMI and lipid profiles. These results show that epigenetic regulation may be involved in the alteration of adipose tissue functions in obesity.

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Weight loss after Roux-En-Y gastric bypass surgery reveals skeletal muscle DNA methylation changes

Cited by 10 publications

References 46 publications

Can Exercise Training Alter Human Skeletal Muscle DNA Methylation?

Can Exercise Training Alter Human Skeletal Muscle DNA Methylation?

Molecular remodeling of adipose tissue is associated with metabolic recovery after weight loss surgery

DNA Methylation Remodeling after Bariatric Surgery Correlates with Clinical Parameters

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