Changes in SCD gene DNA methylation after bariatric surgery in morbidly obese patients are associated with free fatty acids

Morcillo, Sonsoles; Martín‐Núñez, Gracia María; García‐Serrano, Sara; Gutiérrez-Repiso, Carolina; Rodríguez‐Pacheco, Francisca; Valdés, Sergio; Gonzalo, Montserrat; Rojo‐Martínez, Gemma; Moreno-Ruiz, Francisco J.; Rodríguez‐Cañete, Alberto; Tinahones, Francisco J.; Garcı́a-Fuentes, Eduardo

doi:10.1038/srep46292

Cited by 15 publications

(9 citation statements)

References 39 publications

(51 reference statements)

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“…Our data suggests restoration of the "severe obesity" DNA methylation patterns 12 months after surgery to the epigenetic profiles found in general populations. In agreement with these observations, DNA methylation levels of the SCD gene promoter were found to be lower in morbidly obese subjects (n = 120) before bariatric surgery but increased 6 months after RYGB to similar levels as in the control group (n = 30, BMI similar to after surgery group) [63].…”

Section: Epigenetic Changes After Bariatric Surgerysupporting

confidence: 82%

The effects of bariatric surgery on clinical profile, DNA methylation, and ageing in severely obese patients

et al. 2020

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Background: Severe obesity is a growing, worldwide burden and conventional therapies including radical change of diet and/or increased physical activity have limited results. Bariatric surgery has been proposed as an alternative therapy showing promising results. It leads to substantial weight loss and improvement of comorbidities such as type 2 diabetes. Increased adiposity is associated with changes in epigenetic profile, including DNA methylation. We investigated the effect of bariatric surgery on clinical profile, DNA methylation, and biological age estimated using Horvath's epigenetic clock. Results:To determine the impact of bariatric surgery and subsequent weight loss on clinical traits, a cohort of 40 severely obese individuals (BMI = 30-73 kg/m 2 ) was examined at the time of surgery and at three follow-up visits, i.e., 3, 6, and 12 months after surgery. The majority of the individuals were women (65%) and the mean age at surgery was 45.1 ± 8.1 years. We observed a significant decrease over time in BMI, fasting glucose, HbA1c, HOMA-IR, insulin, total cholesterol, triglycerides, LDL and free fatty acids levels, and a significant small increase in HDL levels (all p values < 0.05). Epigenome-wide association analysis revealed 4857 differentially methylated CpG sites 12 months after surgery (at Bonferroni-corrected p value < 1.09 × 10 −7 ). Including BMI change in the model decreased the number of significantly differentially methylated CpG sites by 51%. Gene set enrichment analysis identified overrepresentation of multiple processes including regulation of transcription, RNA metabolic, and biosynthetic processes in the cell. Bariatric surgery in severely obese patients resulted in a decrease in both biological age and epigenetic age acceleration (EAA) (mean = − 0.92, p value = 0.039). Conclusions: Our study shows that bariatric surgery leads to substantial BMI decrease and improvement of clinical outcomes observed 12 months after surgery. These changes explained part of the association between bariatric surgery and DNA methylation. We also observed a small, but significant improvement of biological age. These epigenetic changes may be modifiable by environmental lifestyle factors and could be used as potential biomarkers for obesity and in the future for obesity related comorbidities.

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Section: Epigenetic Changes After Bariatric Surgerysupporting

confidence: 82%

The effects of bariatric surgery on clinical profile, DNA methylation, and ageing in severely obese patients

et al. 2020

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“…Additionally, the methylation level of the genes involved in metabolic pathways also showed changes after bariatric surgery. The methylation levels of the stearoyl CoA desaturase-1 (SCD) gene promoter were decreased in morbidly obese individuals before bariatric surgery, and increased 6 months after RYGB, resembling those observed in individuals in the control group (98). SCD is an endoplasmic reticulum-bound enzyme that transforms different saturated fatty acids into monounsaturated fatty acids (99).…”

Section: Changes In Epigenetic Marks After Bariatric Surgerymentioning

confidence: 85%

Obesity-Related Epigenetic Changes After Bariatric Surgery

Izquierdo

Crujeiras

2019

Front. Endocrinol.

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Objective: In recent years, an increasing number of studies have begun focusing on epigenetics as a link between environmental factors and a greater predisposition to the development of obesity and its comorbidities. An important challenge in this field is the evaluation of the possibility of the reversal of obesity-related epigenetic marks by means of therapy to induce weight loss and if the beneficial effects of therapy in reducing obesity are mediated by epigenetic mechanisms. We aimed to offer an outline of the current results regarding to the impact of bariatric surgery on epigenetic regulation, as well as to show if the beneficial effect of this intervention could be mediated by epigenetic mechanisms. Methods: A review of the scientific publications in PubMed was performed by using key words related to obesity, epigenetics and bariatric surgery to provide an update of recent findings in this area of research. The most relevant and recently published articles and abstracts were selected to frame this review. Results: Previous studies have demonstrated the presence of differential DNA methylation after bariatric surgery and the differential expression of non-coding RNAs. Therefore, epigenetic regulation could mediate the benefit of bariatric surgery on body weight and the metabolic disturbances associated with excess body weight, such as insulin resistance, hypertension, and cardiovascular disease. This evidence is relatively new as epigenetic regulation was first evaluated in the obesity field only a few years ago. However, there is an urgent need to perform longitudinal studies to evaluate the capacity of epigenetic marks in the prediction of bariatric surgery response. Conclusions: Bariatric surgery appears to be capable of partially reversing the obesity-related epigenome. The identification of potential epigenetic biomarkers predictive for the success of bariatric surgery may open new doors to personalized therapy for severe obesity.

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“…The absence of SCD has been related with an improvement of metabolic syndrome features in mice [54]. Furthermore, a decrease in SCD DNA methylation has been associated with weight loss in both a dietary intervention study and after bariatric surgery [55,56].…”

Section: Discussionmentioning

confidence: 99%

Altered Adipose Tissue DNA Methylation Status in Metabolic Syndrome: Relationships Between Global DNA Methylation and Specific Methylation at Adipogenic, Lipid Metabolism and Inflammatory Candidate Genes and Metabolic Variables

Castellano‐Castillo

Moreno-Indias

Sánchez-Alcoholado

et al. 2019

JCM

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Metabolic syndrome (MetS) has been postulated to increase the risk for type 2 diabetes, cardiovascular disease and cancer. Adipose tissue (AT) plays an important role in metabolic homeostasis, and AT dysfunction has an active role in metabolic diseases. MetS is closely related to lifestyle and environmental factors. Epigenetics has emerged as an interesting landscape to evaluate the possible interconnection between AT and metabolic disease, since it can be modulated by environmental factors and metabolic status. The aim of this study was to determine whether MetS has an impact on the global DNA methylation pattern and the DNA methylation of several genes related to adipogenesis (PPARG, PPARA), lipid metabolism (RXRA, SREBF2, SREBF1, SCD, LPL, LXRb), and inflammation (LRP1 C3, LEP and TNF) in visceral adipose tissue. LPL and TNF DNA methylation values were significantly different in the control-case comparisons, with higher and lower methylation respectively in the MetS group. Negative correlations were found between global DNA methylation (measured by LINE-1 methylation levels) and the metabolic deterioration and glucose levels. There were associations among variables of MetS, BMI, and HOMA-IR with DNA methylation at several CpG positions for the studied genes. In particular, there was a strong positive association between serum triglyceride levels (TG) with PPARA and LPL methylation levels. TNF methylation was negatively associated with the metabolic worsening and could be an important factor in preventing MetS occurrence according to logistic regression analysis. Therefore, global DNA methylation and methylation at specific genes related to adipogenesis, lipid metabolism and inflammation are related to the etiology of MetS and might explain in part some of the features associated to metabolic disorders.

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Changes in SCD gene DNA methylation after bariatric surgery in morbidly obese patients are associated with free fatty acids

Cited by 15 publications

References 39 publications

The effects of bariatric surgery on clinical profile, DNA methylation, and ageing in severely obese patients

The effects of bariatric surgery on clinical profile, DNA methylation, and ageing in severely obese patients

Obesity-Related Epigenetic Changes After Bariatric Surgery

Altered Adipose Tissue DNA Methylation Status in Metabolic Syndrome: Relationships Between Global DNA Methylation and Specific Methylation at Adipogenic, Lipid Metabolism and Inflammatory Candidate Genes and Metabolic Variables

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