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A single FTO gene variant rs9939609 is associated with weight change and insulin resistance improvement in response to a robotic sleeve gastrectomy in individuals with severe obesity

  • Daniel A. de Luis
    Correspondence
    Correspondence: Daniel A. de Luis, M.D.Ph., Endocrinology and Nutrition Research Center, School of Medicine, Valladolid University, C/Los perales 16 Simancas, 47130 Valladolid, Spain.
    Affiliations
    Endocrinology and Nutrition Research Center, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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  • Olatz Izaola
    Affiliations
    Endocrinology and Nutrition Research Center, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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  • David Primo
    Affiliations
    Endocrinology and Nutrition Research Center, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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  • Juan José López
    Affiliations
    Endocrinology and Nutrition Research Center, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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  • David Pacheco
    Affiliations
    Endocrinology and Nutrition Research Center, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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Published:November 07, 2022DOI:https://doi.org/10.1016/j.soard.2022.10.035

      Abstract

      Background

      Genetic mechanisms have been involved in the weight response secondary to bariatric surgery.

      Objective

      The aim of our study was to evaluate the effects of the rs9939609 genetic variant on weight loss and metabolic parameters after sleeve gastrectomy.

      Setting

      Xxx.

      Methods

      A total of 95 participants were enrolled. Co-morbidities, biochemical evaluation, and anthropometric parameters were registered before and after 3-, 6-, and 12-month follow-up. Genotype of the rs9939609 fat mass and obesity-associated (FTO) gene was evaluated.

      Results

      We grouped the participants into 2 groups: carriers of A allele (TA+AA, 69.5%) and noncarriers of A allele (TT, 30.5%). We detected a statistically significant reduction of blood pressure, biochemical, and anthropometric parameters at 3 times during follow-up. After 6 months, changes of some parameters were greater in non-A allele carriers: weight (–39.6 + 4.0 kg versus –24.6 + 2.8 kg; P = .02), waist circumference (–21.1 + 2.1 cm versus –16.2 + 1.8 cm; P = .04), insulin (–12.3 + .9 mUI/L versus –8.9.1 + .2 mUI/L; P = .02), and homeostasis model assessment of insulin resistance (–3.1 + .1 units versus –2.3 + .1 units; P = .02 ). After 12 months, changes of the aforementioned parameters remained greater in non-A allele carriers. The percentage of participants with diabetes diminished earlier in the non-A allele carriers than A allele carriers at 6-month follow-up. The percentage of participants with diabetes at the end of the study was lower in non-A allele carriers (3.4% versus 12.1%; P = .02).

      Conclusions

      Our data suggest that non-A allele carriers of the genetic variant (rs9939609) of the FTO gene showed a better improvement of anthropometric and insulin levels in non-A allele carriers after a robotic sleeve gastrectomy. Both improvements are associated with a lower percentage of participants with diabetes at 12 months.

      Key words

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      References

        • Kaplan S.A.
        Re: National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants.
        J Urol. 2011; 186: 1982-1983
        • Gutiérrez-Fisac J.L.
        Prevalence of general and abdominal obesity in the adult population of Spain, 2008-2010: the ENRICA study.
        Obes Rev. 2012; 13: 388-392
        • Sarwer D.B.
        • Steffen K.J.
        Quality of life, body image and sexual functioning in bariatric surgery patients.
        Eur Eat Disord Rev. 2015; 23: 504-508
        • Cui B.
        • Zhu L.
        • Zhu S.
        Effects of Roux-en-Y gastric bypass versus sleeve gastrectomy on body composition for patients with a BMI > 35 kg/m2 at 1 year after surgery.
        Obes Surg. 2022; 32: 1658-1666
        • Thomas S.
        • Schauer P.
        Bariatric surgery and the gut hormone response.
        Nutr Clin Pract. 2010; 25: 175-182
        • Clifton P.
        Diabetes: treatment of type 2 diabetes mellitus with bariatric surgery.
        Nat Rev Endocrinol. 2010; 6: 191-193
        • Pacheco D.
        • Izaola O.
        • Primo D.
        • de Luis D.
        Role of the variant rs3774261 of adiponectin gene on adiponectin levels and ratio adiponectin/leptin after biliopancreatic diversion in morbid obese subjects.
        Eur Rev Med Pharmacol Sci. 2022; 26: 240-248
        • Yang J.
        • Loos R.J.F.
        • Powell J.E.
        • et al.
        FTO genotype is associated with phenotypic variability of body mass index.
        Nature. 2012; 490: 267-272
        • Frayling T.M.
        • Timpson N.J.
        • Weedon M.N.
        • et al.
        A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.
        Science. 2007; 316: 889-894
        • Church C.
        • Moir L.
        • McMurray F.
        • et al.
        Overexpression of FTO leads to increased food intake and results in obesity.
        Nat Genet. 2010; 42: 1086-1092
        • Franks P.W.
        • Jablonski K.A.
        • Delahanty L.M.
        • et al.
        Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program.
        Diabetologia. 2008; 51: 2214-2223
        • Lappalainen T.J.
        • Tolppanen A.M.
        • Kolehmainen M.
        • et al.
        The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: the Finnish Diabetes Prevention Study.
        Obesity (Silver Spring). 2009; 17: 832-836
        • Razquin C.
        • Martinez J.A.
        • Martinez-Gonzalez M.A.
        • Bes-Rastrollo M.
        • Fernández-Crehuet M.
        • Marti A.
        A 3-year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes.
        Int J of Obesity. 2010; 34: 266-272
        • Liou T.H.
        • Chen H.
        • Wang W.
        • et al.
        ESR1, FTO and UCP2 genes interact with bariatric surgery affecting weight loss and glycemic control in severely obese patients.
        Obes Surg. 2011; 21: 1758-1765
        • Sarzynski M.A.
        • Jacobson P.
        • Rankinen T.
        • et al.
        Associations of markers in 11 obesity candidate genes with maximal weight loss and weight regain in the SOS bariatric surgery cases.
        Int J of Obes. 2011; 35: 676-683
        • de Luis D.A.
        • Aller R.
        • Conde R.
        • Izaola O.
        • Pacheco D.
        • Sagrado M.G.
        • Primo D.
        Effects of RS9939609 gene variant in FTO gene on weight loss and cardiovascular risk factors after biliopancreatic diversion surgery.
        J Gastrointest Surg. 2012; 16: 1194-1198
        • Balasar Ö.
        • Çakır T.
        • Erkal Ö.
        • et al.
        The effect of rs9939609 FTO gene polymorphism on weight loss after laparoscopic sleeve gastrectomy.
        Surg Endosc. 2016; 30: 121-125
        • Friedewald W.T.
        • Levy R.J.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge.
        Clin Chem. 1972; 18: 499-502
        • Mathews D.R.
        • Hosker J.P.
        • Rudenski A.S.
        • Naylor B.A.
        • Treacher D.F.
        Homeostasis model assessment: insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 1985; 28: 412-414
        • Dzamko N.
        • van Denderen B.J.
        • Hevener A.L.
        • et al.
        AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance.
        J Biol Chem. 2010; 285: 115-122
        • Saiki A.
        • Olsson M.
        • Jernås M.
        • et al.
        Tenomodulin is highly expressed in adipose tissue, increased in obesity, and down-regulated during diet-induced weight loss.
        J Clin Endocrinol Metab. 2009; 94: 3987-3994
        • Toledo F.G.
        • Menshikova E.V.
        • Ritov V.B.
        • et al.
        Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes.
        Diabetes. 2007; 56: 2142-2147
        • Gu L.
        • Lin K.
        • Du N.
        • Ng D.M.
        • Lou D.
        • Chen P.
        Differences in the effects of laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass on gut hormones: systematic and meta-analysis.
        Surg Obes Relat Dis. 2021; 17: 444-455
        • Costford S.R.
        • Crawford S.A.
        • Dent R.
        • McPherson R.
        • Harper M.E.
        Increased susceptibility to oxidative damage in post-diabetic human myotubes.
        Diabetologia. 2009; 52: 2405-2415
        • Rajkumar A.
        • Liaghati A.
        • Chan J.
        • et al.
        ACSL5 genotype influence on fatty acid metabolism: a cellular, tissue, and whole-body study.
        Metabolism. 2018; 83: 271-279
        • Novais P.F.S.
        • Crisp A.H.
        • Leandro-Merhi V.A.
        • Cintra R.M.G.
        • Rasera Jr., I.
        • Oliveira M.R.M.
        Genetic polymorphisms are not associated with energy intake 1 year after Roux-en-Y gastric bypass in women.
        J Hum Nutr Diet. 2022; 35: 739-747
        • Rodrigues G.K.
        • Resende C.M.
        • Durso D.F.
        • et al.
        A single FTO gene variant rs9939609 is associated with body weight evolution in a multiethnic extremely obese population that underwent bariatric surgery.
        Nutrition. 2015; 31: 1344-1350
        • Kops N.L.
        • Vivan M.A.
        • Horvath J.D.C.
        • de Castro M.L.D.
        • Friedman R.
        FABP2, LEPR223, LEP656, and FTO polymorphisms: effect on weight loss 2 years after bariatric surgery.
        Obes Surg. 2018; 28: 2705-2711
        • Bandstein M.
        • Schultes B.
        • Ernst B.
        • Thurnheer M.
        • Schiöth H.B.
        • Benedict C.
        The role of FTO and vitamin D for the weight loss effect of Roux-en-Y gastric bypass surgery in obese patients.
        Obes Surg. 2015; 25: 2071-2077
        • Dusso A.S.
        • Brown A.J.
        • Slatopolsky E.
        Vitamin D.
        Am J Physiol Renal Physiol. 2005; 289: F8-F28
        • Wang C.Y.
        • Liu K.H.
        • Tsai M.L.
        • et al.
        FTO variants are associated with ANGPTL4 abundances and correlated with body weight reduction after bariatric surgery.
        Obes Res Clin Pract. 2020; 14: 257-263

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