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

Sonsoles Morcillo, Gracia Mª Martín-Núñez, Sara García-Serrano, Carolina Gutierrez-Repiso, Francisca Rodriguez-Pacheco, Sergio Valdes, Montserrat Gonzalo, Gemma Rojo-Martinez, Francisco J Moreno-Ruiz, Alberto Rodriguez-Cañete, Francisco Tinahones, Eduardo García-Fuentes, Sonsoles Morcillo, Gracia Mª Martín-Núñez, Sara García-Serrano, Carolina Gutierrez-Repiso, Francisca Rodriguez-Pacheco, Sergio Valdes, Montserrat Gonzalo, Gemma Rojo-Martinez, Francisco J Moreno-Ruiz, Alberto Rodriguez-Cañete, Francisco Tinahones, Eduardo García-Fuentes

Abstract

Stearoyl CoA Desaturase-1 (SCD) is considered as playing an important role in the explanation of obesity. The aim of this study was to evaluate whether the DNA methylation SCD gene promoter is associated with the metabolic improvement in morbidly obese patients after bariatric surgery. The study included 120 subjects with morbid obesity who underwent a laparoscopic Roux-en Y gastric by-pass (RYGB) and a control group of 30 obese subjects with a similar body mass index (BMI) to that found in morbidly obese subjects six months after RYGB. Fasting blood samples were obtained before and at six months after RYGB. DNA methylation was measured by pyrosequencing technology. DNA methylation levels of the SCD gene promoter were lower in morbidly obese subjects before bariatric surgery but increased after RYGB to levels similar to those found in the control group. Changes of DNA methylation SCD gene were associated with the changes of free fatty acids levels (r = -0.442, p = 0.006) and HOMA-IR (r = -0.249, p = 0.035) after surgery. RYGB produces an increase in the low SCD methylation promoter levels found in morbidly obese subjects. This change of SCD methylation levels is associated with changes in FFA and HOMA-IR.

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1. SCD methylation levels (%).
Figure 1. SCD methylation levels (%).
(A) SCD methylation levels (%) in the control group and morbidly obese subjects before bariatric surgery. (B) SCD methylation levels (%) in morbidly obese subjects before and six months after bariatric surgery. Kruskall-Wallis test was used to compare means between control group and morbidly obese subjects before surgery. Wilcoxon test was performed to compare means between morbidly obese subjects before and six months after bariatric surgery.
Figure 2
Figure 2
Association between the changes of SCD gene promoter methylation levels (%) with the change of serum free fatty acids level (FFA) (%) (A), and with the change of HOMA-IR level (%) (B) after RYGB; and with the change of weight (%) after RYGB in those morbidly obese subjects who lost a greater percentage of weight (above percentile 75th) (C).

References

    1. Soriguer F. et al.. Obesity and the metabolic syndrome in Mediterranean countries: a hypothesis related to olive oil. Mol Nutr Food Res 51, 1260–1267 (2007).
    1. Ntambi J. M. & Miyazaki M. Regulation of stearoyl-CoA desaturases and role in metabolism. Prog. Lipid Res. 43, 91–104 (2004).
    1. Rahman S. M. et al.. Stearoyl-CoA desaturase 1 deficiency increases insulin signaling and glycogen accumulation in brown adipose tissue. Am J Physiol Endocrinol Metab 288, E381–7 (2005).
    1. García-Serrano S. et al.. Stearoyl-CoA desaturase-1 is associated with insulin resistance in morbidly obese subjects. Mol. Med. 17, 273–80 (2011).
    1. Ntambi J. M. et al.. Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 99, 11482–11486 (2002).
    1. Flowers J. B. et al.. Loss of stearoyl-CoA desaturase-1 improves insulin sensitivity in lean mice but worsens diabetes in leptin-deficient obese mice. Diabetes 56, 1228–39 (2007).
    1. Sjöström L. et al.. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N. Engl. J. Med. 351, 2683–93 (2004).
    1. Garrido-Sanchez L. et al.. Bypass of the duodenum improves insulin resistance much more rapidly than sleeve gastrectomy. Surg. Obes. Relat. Dis. 8, 145–50 (2012).
    1. Buchwald H. et al.. Weight and Type 2 Diabetes after Bariatric Surgery: Systematic Review and Meta-analysis. Am. J. Med. 122, 248–256.e5 (2009).
    1. Rubino F. et al.. The Mechanism of Diabetes Control After Gastrointestinal Bypass Surgery Reveals a Role of the Proximal Small Intestine in the Pathophysiology of Type 2 Diabetes. Ann. Surg. 244, 741–749 (2006).
    1. Falkén Y., Hellström P. M., Holst J. J. & Näslund E. Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptides. J. Clin. Endocrinol. Metab. 96, 2227–35 (2011).
    1. Van Dijk S. J. et al.. Epigenetics and human obesity. Int. J. Obes. (Lond). 39, 85–97 (2015).
    1. Rönn T. & Ling C. DNA methylation as a diagnostic and therapeutic target in the battle against Type 2 diabetes. Epigenomics 7, 451–60 (2015).
    1. Barrès Romain & Zierath Juleen R. The role of diet and exercise in the transgenerational epigenetic landscape of T2DM. Nat. Rev. Endocrinol. 12, 441–451 (2016).
    1. Kirchner H. et al.. Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass. Surg. Obes. Relat. Dis. 10, 671–678 (2014).
    1. Barres R. et al.. Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation. Cell Rep. 3, 1020–1027 (2013).
    1. Benton M. C. et al.. An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss. Genome Biol. 16, 8 (2015).
    1. Huang Y.-T. et al.. Epigenetic patterns in successful weight loss maintainers: a pilot study. Int. J. Obes. (Lond). 39, 865–8 (2015).
    1. Cordero P. et al.. Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet. J Physiol Biochem 67, 463–470 (2011).
    1. Schwenk R. et al.. Diet-dependent Alterations of Hepatic Scd1 Expression are Accompanied by Differences in Promoter Methylation. Horm. Metab. Res. 45, 786–794 (2013).
    1. Martín-Núñez G. M. et al.. Methylation levels of the SCD1 gene promoter and LINE-1 repeat region are associated with weight change: an intervention study. Mol. Nutr. Food Res. 58, 1528–36 (2014).
    1. Liu X., Strable M. S. & Ntambi J. M. Stearoyl CoA desaturase 1: role in cellular inflammation and stress. Adv. Nutr. 2, 15–22 (2011).
    1. Cummings D. E., Overduin J. & Foster-Schubert K. E. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J. Clin. Endocrinol. Metab. 89, 2608–15 (2004).
    1. Garrido-Sánchez L. et al.. De novo lipogenesis in adipose tissue is associated with course of morbid obesity after bariatric surgery. PLoS One 7, e31280 (2012).
    1. Nilsson E. K. et al.. Roux-en Y gastric bypass surgery induces genome-wide promoter-specific changes in DNA methylation in whole blood of obese patients. PLoS One 10, e0115186 (2015).
    1. Alegria-Torres J. A., Baccarelli A. & Bollati V. Epigenetics and lifestyle. Epigenomics 3, 267–277 (2011).
    1. Barrès R. et al.. Non-CpG Methylation of the PGC-1α Promoter through DNMT3B Controls Mitochondrial Density. Cell Metab. 10, 189–198 (2009).
    1. Sessler A. M., Kaur N., Palta J. P. & Ntambi J. M. Regulation of stearoyl-CoA desaturase 1 mRNA stability by polyunsaturated fatty acids in 3T3-L1 adipocytes. J. Biol. Chem. 271, 29854–8 (1996).
    1. Shen W. et al.. Epigenetic modification of the leptin promoter in diet-induced obese mice and the effects of N-3 polyunsaturated fatty acids. Sci. Rep. 4, 5282 (2014).
    1. Okamura M., Inagaki T., Tanaka T. & Sakai J. Role of histone methylation and demethylation in adipogenesis and obesity. Organogenesis 6, 24–32 (2010).
    1. Hall E. et al.. Effects of palmitate on genome-wide mRNA expression and DNA methylation patterns in human pancreatic islets. BMC Med. 12, 103 (2014).
    1. De la Rocha C. et al.. Associations between whole peripheral blood fatty acids and DNA methylation in humans. Sci. Rep. 6, 25867 (2016).
    1. Peter A. et al.. Hepatic lipid composition and stearoyl-coenzyme A desaturase 1 mRNA expression can be estimated from plasma VLDL fatty acid ratios. Clin. Chem. 55, 2113–20 (2009).
    1. Skuladottir G. V., Nilsson E. K., Mwinyi J. & Schiöth H. B. One-night sleep deprivation induces changes in the DNA methylation and serum activity indices of stearoyl-CoA desaturase in young healthy men. Lipids Health Dis. 15, 137 (2016).
    1. Mill J. & Heijmans B. T. From promises to practical strategies in epigenetic epidemiology. Nat. Rev. Genet. 14, 585–94 (2013).
    1. Murri M. et al.. Changes in oxidative stress and insulin resistance in morbidly obese patients after bariatric surgery. Obes. Surg. 20, 363–8 (2010).
    1. Garcia-Fuentes E. et al.. PPARgamma expression after a high-fat meal is associated with plasma superoxide dismutase activity in morbidly obese persons. Obesity (Silver Spring). 18, 952–8 (2010).
    1. Soriguer F. et al.. Changes in the serum composition of free-fatty acids during an intravenous glucose tolerance test. Obesity (Silver Spring). 17, 10–5 (2009).
    1. Li L. C. & Dahiya R. MethPrimer: designing primers for methylation PCRs. Bioinformatics 18, 1427–1431 (2002).
    1. Team R. C. R.: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. at (2014).

Source: PubMed

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