Top

Obesity Surgery

Published in:

01-11-2011 | Clinical Research

ESR1, FTO, and UCP2 Genes Interact with Bariatric Surgery Affecting Weight Loss and Glycemic Control in Severely Obese Patients

Authors: Tsan-Hon Liou, Hsin-Hung Chen, Weu Wang, Shu-Fen Wu, Yi-Chih Lee, Wei-Shiung Yang, Wei-Jei Lee

Published in: Obesity Surgery | Issue 11/2011

Abstract

Background

Significant variability in weight loss and glycemic control has been observed in obese patients receiving bariatric surgery. Genetic factors may play a role in the different outcomes.

Methods

Five hundred and twenty severely obese patients with body mass index (BMI) ≥35 were recruited. Among them, 149 and 371 subjects received laparoscopic adjustable gastric banding (LAGB) and laparoscopic mini-gastric bypass (LMGB), respectively. All individuals were genotyped for five obesity-related single nucleotide polymorphisms on ESR1, FTO, PPARγ, and UCP2 genes to explore how these genes affect weight loss and glycemic control after bariatric surgery at the 6th month.

Results

Obese patients with risk genotypes on rs660339-UCP2 had greater decrease in BMI after LAGB compared to patients with non-risk genotypes (−7.5 vs. −6 U, p = 0.02). In contrast, after LMGB, obese patients with risk genotypes on either rs712221-ESR1 or rs9939609-FTO had significant decreases in BMI (risk vs. non-risk genotype, −12.5 vs. −10.0 U on rs712221, p = 0.02 and −12.1 vs. −10.6 U on rs9939609, p = 0.04) and a significant amelioration in HbA1c levels (p = 0.038 for rs712221 and p < 0.0001 for rs9939609). The synergic effect of ESR1 and FTO genes on HbA1c amelioration was greater (−1.54%, p for trend <0.001) than any of these genes alone in obese patients receiving LMGB.

Conclusions

The genetic variants in the ESR, FTO, and UCP2 genes may be considered as a screening tool prior to bariatric surgery to help clinicians predict weight loss or glycemic control outcomes for severely obese patients.

DiPietro L, Dziura J, Yeckel CW. Specific relation between abdominal obesity and early-phase hyperglycemia is modulated by hepatic insulin resistance in healthy older women. Diabetes Care. 2010;33(1):165–7.PubMedCrossRef

Bonora E, Brangani C, Pichiri I. Abdominal obesity and diabetes. G Ital Cardiol Rome. 2008;9(4 Suppl 1):40S–53S.PubMed

Pan WH, Flegal KM, Chang HY, et al. Body mass index and obesity-related metabolic disorders in Taiwanese and US whites and blacks: implications for definitions of overweight and obesity for Asians. Am J Clin Nutr. 2004;79(1):31–9.PubMed

Kashyap SR, Gatmaitan P, Brethauer S, et al. Bariatric surgery for type 2 diabetes: weighing the impact for obese patients. Cleve Clin J Med. 2010;77(7):468–76.PubMedCrossRef

Lee WJ, Ser KH, Chong K, et al. Laparoscopic sleeve gastrectomy for diabetes treatment in nonmorbidly obese patients: efficacy and change of insulin secretion. Surgery. 2010;147(5):664–9.PubMedCrossRef

Dixon JB, O’Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA. 2008;299(3):316–23.PubMedCrossRef

Foster GD, Borradaile KE, Vander Veur SS, et al. The effects of a commercially available weight loss program among obese patients with type 2 diabetes: a randomized study. Postgrad Med. 2009;121(5):113–8.PubMedCrossRef

Martins C, Strømmen M, Stavne OA, et al. Bariatric surgery versus lifestyle interventions for morbid obesity-changes in body weight, risk factors and comorbidities at 1 year. Obes Surg (2011). Accessed 9 Apr ISSN:1708-0428 (Electronic).

Jaunoo SS, Southall PJ. Bariatric surgery. Int J Surg. 2010;8(2):86–9.PubMedCrossRef

10.

Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724–37.PubMedCrossRef

11.

Lee WJ, Chong K, Lee YC, et al. Effects of obesity surgery on type 2 diabetes mellitus Asian patients. World J Surg. 2009;33(9):1895–903.PubMedCrossRef

12.

Thomas S, Schauer P. Bariatric surgery and the gut hormone response. Nutr Clin Pract. 2010;25(2):175–82.PubMedCrossRef

13.

Maggard MA, Shugarman LR, Suttorp M, et al. Meta-analysis: surgical treatment of obesity. Ann Intern Med. 2005;142(7):547–59.PubMed

14.

Lee YC, Lee WJ, Lin WC, et al. Obesity and the decision tree: predictors of sustained weight loss after bariatric surgery. Hepatogastroenterology. 2009;56(96):1745–9.PubMed

15.

Clifton P. Diabetes: treatment of type 2 diabetes mellitus with bariatric surgery. Nat Rev Endocrinol. 2010;6(4):191–3.PubMedCrossRef

16.

Chen HH, Lee WJ, Wang W, et al. Ala55Val polymorphism on UCP2 gene predicts greater weight loss in morbidly obese patients undergoing gastric banding. Obes Surg. 2007;17(7):926–33.PubMedCrossRef

17.

Chen HH, Lee WJ, Fann CS, et al. Severe obesity is associated with novel single nucleotide polymorphisms of the ESR1 and PPARgamma locus in Han Chinese. Am J Clin Nutr. 2009;90(2):255–62.PubMedCrossRef

18.

Chang YC, Liu PH, Lee WJ, et al. Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes. 2008;57(8):2245–52.PubMedCrossRef

19.

Huang Q, Wang TH, Lu WS, et al. Estrogen receptor alpha gene polymorphism associated with type 2 diabetes mellitus and the serum lipid concentration in Chinese women in Guangzhou. Chin Med J Engl. 2006;119(21):1794–801.PubMed

20.

Kovacs P, Ma L, Hanson RL, et al. Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians. Diabetologia. 2005;48(11):2292–5.PubMedCrossRef

21.

Saleh MC, Wheeler MB, Chan CB. Uncoupling protein-2: evidence for its function as a metabolic regulator. Diabetologia. 2002;45(2):174–87.PubMedCrossRef

22.

Picard F, Auwerx J. PPAR(gamma) and glucose homeostasis. Annu Rev Nutr. 2002;22:167–97.PubMedCrossRef

23.

Carmen GY, Victor SM. Signalling mechanisms regulating lipolysis. Cell Signal. 2006;18(4):401–8.PubMedCrossRef

24.

Rosen ED, Sarraf P, Troy AE, et al. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell. 1999;4(4):611–7.PubMedCrossRef

25.

Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem. 1987;162(1):156–9.PubMedCrossRef

26.

Puissant C, Houdebine LM. An improvement of the single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Biotechniques. 1990;8(2):148–9.PubMedCrossRef

27.

Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction: twenty-something years on. Nat Protoc. 2006;1(2):581–5.PubMedCrossRef

28.

Tanyi M, Kanyári Z, Juhász B, et al. Surgical treatment of morbid obesity. Chir Bucur. 2007;102(2):131–41.

29.

Mittempergher F, Di Betta E, Crea N, et al. Our experience in selecting patients for bariatric surgery. Ann Ital Chir. 2007;78(6):487–92.PubMed

30.

Lee WJ, Yu PJ, Wang W, et al. Laparoscopic Roux-en-Y versus mini-gastric bypass for the treatment of morbid obesity: a prospective randomized controlled clinical trial. Ann Surg. 2005;242(1):20–8.PubMedCrossRef

31.

Wang W, Wei PL, Lee YC, et al. Short-term results of laparoscopic mini-gastric bypass. Obes Surg. 2005;15(5):648–54.PubMedCrossRef

32.

Favretti F, Cadiere GB, Segato G, et al. Laparoscopic banding: selection and technique in 830 patients. Obes Surg. 2002;12(3):385–90.PubMedCrossRef

33.

Angrisani L, Furbetta F, Doldi SB, et al. Lap band adjustable gastric banding system: the Italian experience with 1863 patients operated on 6 years. Surg Endosc. 2003;17(3):409–12.PubMedCrossRef

34.

Dargent J. Surgical treatment of morbid obesity by adjustable gastric band: the case for a conservative strategy in the case of failure—a 9-year series. Obes Surg. 2004;14(7):986–90.PubMedCrossRef

35.

Wang W, Huang MT, Wei PL, et al. Laparoscopic mini-gastric bypass for failed vertical banded gastroplasty. Obes Surg. 2004;14(6):777–82.PubMedCrossRef

36.

Lee WJ, Wang W, Lee YC, et al. Effect of laparoscopic mini-gastric bypass for type 2 diabetes mellitus: comparison of BMI > 35 and <35 kg/m². J Gastrointest Surg. 2008;12(5):945–52.PubMedCrossRef

37.

Souza RP, De Luca V, Muscettola G, et al. Association of antipsychotic induced weight gain and body mass index with GNB3 gene: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(8):1848–53.PubMedCrossRef

38.

Sartori M, Ceolotto G, Dorigatti F, et al. RGS2 C1114G polymorphism and body weight gain in hypertensive patients. Metabolism. 2008;57(3):421–7.PubMedCrossRef

39.

Dzamko N, van Denderen BJ, Hevener AL, et al. AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance. J Biol Chem. 2010;285(1):115–22.PubMedCrossRef

40.

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(10):3987–94.PubMedCrossRef

41.

Figueroa KP, Farooqi S, Harrup K, et al. Genetic variance in the spinocerebellar ataxia type 2 (ATXN2) gene in children with severe early onset obesity. PLoS ONE. 2009;4(12):e8280.PubMedCrossRef

42.

Hsiao DJ, Wu LS, Huang SY, et al. Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene. Pharmacogenet Genomics. 2009;19(9):730–3.PubMedCrossRef

43.

Nannipieri M, Cecchetti F, Anselmino M, et al. Expression of thyrotropin and thyroid hormone receptors in adipose tissue of patients with morbid obesity and/or type 2 diabetes: effects of weight loss. Int J Obes Lond. 2009;33(9):1001–6.PubMedCrossRef

44.

Tanofsky-Kraff M, McDuffie JR, Yanovski SZ, et al. The FTO gene rs9939609 obesity-risk allele and loss of control over eating. Am J Clin Nutr. 2009;90(6):1483–8.PubMedCrossRef

45.

Toledo FG, Menshikova EV, Ritov VB, 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(8):2142–7.PubMedCrossRef

46.

Lehmann R, Vokac A, Niedermann K, et al. Loss of abdominal fat and improvement of the cardiovascular risk profile by regular moderate exercise training in patients with NIDDM. Diabetologia. 1995;38(11):1313–9.PubMedCrossRef

47.

Zaninovich AA. Role of uncoupling proteins UCP1, UCP2 and UCP3 in energy balance, type 2 diabetes and obesity. Synergism with the thyroid. Med B Aires. 2005;65(2):163–9.

48.

Le Fur S, Le Stunff C, Dos Santos C, et al. The common −866G/A polymorphism in the promoter of uncoupling protein 2 is associated with increased carbohydrate and decreased lipid oxidation in juvenile obesity. Diabetes. 2004;53(1):235–9.PubMedCrossRef

49.

Yanovski JA, Diament AL, Sovik KN, et al. Associations between uncoupling protein 2, body composition, and resting energy expenditure in lean and obese African American, white, and Asian children. Am J Clin Nutr. 2000;71(6):1405–20.PubMed

50.

Buemann B, Schierning B, Toubro S, et al. The association between the val/ala-55 polymorphism of the uncoupling protein 2 gene and exercise efficiency. Int J Obes Relat Metab Disord. 2001;25(4):467–71.PubMedCrossRef

51.

Ukkola O, Tremblay A, Sun G, et al. Genetic variation at the uncoupling protein 1, 2 and 3 loci and the response to long-term overfeeding. Eur J Clin Nutr. 2001;55(11):1008–15.PubMedCrossRef

52.

Astrup A, Toubro S, Dalgaard L, et al. Impact of the v/v 55 polymorphism of the uncoupling protein 2 gene on 24-h energy expenditure and substrate oxidation. Int J Obes Relat Metab Disord. 1999;23(10):1030–4.PubMedCrossRef

53.

Mulcare DB, Dennin HF, Drenick EJ. Effect of diet on malabsorption after small bowel by-pass. J Am Diet Assoc. 1970;57(4):331–5.PubMed

54.

Folope V, Coeffier M, Dechelotte P. Nutritional deficiencies associated with bariatric surgery. Gastroentérol Clin Biol. 2007;31(4):369–77.PubMedCrossRef

55.

Frayling TM, Timpson NJ, Weedon MN, 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(5826):889–94.PubMedCrossRef

56.

Muller TD, Hinney A, Scherag A, et al. ‘Fat mass and obesity associated’ gene (FTO): no significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents. BMC Med Genet. 2008;9:85.PubMedCrossRef

57.

Peeters A, Beckers S, Verrijken A, et al. Variants in the FTO gene are associated with common obesity in the Belgian population. Mol Genet Metab. 2008;93(4):481–4.PubMedCrossRef

58.

Wahlen K, Sjolin E, Hoffstedt J. The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis. J Lipid Res. 2008;49(3):607–11.PubMedCrossRef

59.

Lee WJ, Wang W. Bariatric surgery: Asia-Pacific perspective. Obes Surg. 2005;15(6):751–7.PubMedCrossRef

60.

Potoczna N, Branson R, Kral JG, et al. Gene variants and binge eating as predictors of comorbidity and outcome of treatment in severe obesity. J Gastrointest Surg. 2004;8(8):971–81. discussion 981–2.PubMedCrossRef

61.

Dias MC, Ribeiro AG, Scabim VM, et al. Dietary intake of female bariatric patients after anti-obesity gastroplasty. Clin Sao Paulo. 2006;61(2):93–8.

62.

Ribeiro AG, Faintuch J, Dias MC, et al. Euglycemia and normolipidemia after anti-obesity gastric bypass. Nutr Hosp. 2009;24(1):32–9.PubMed

63.

Cohen R, Pinheiro JS, Correa JL, et al. Laparoscopic revisional bariatric surgery: myths and facts. Surg Endosc. 2005;19(6):822–5.PubMedCrossRef

Title: ESR1, FTO, and UCP2 Genes Interact with Bariatric Surgery Affecting Weight Loss and Glycemic Control in Severely Obese Patients
Authors: Tsan-Hon Liou
Hsin-Hung Chen
Weu Wang
Shu-Fen Wu
Yi-Chih Lee
Wei-Shiung Yang
Wei-Jei Lee
Publication date: 01-11-2011
Publisher: Springer-Verlag
Published in: Obesity Surgery / Issue 11/2011
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI: https://doi.org/10.1007/s11695-011-0457-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

ESR1, FTO, and UCP2 Genes Interact with Bariatric Surgery Affecting Weight Loss and Glycemic Control in Severely Obese Patients

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 11/2011

Thirty-day Mortality After Bariatric Surgery: Independently Adjudicated Causes of Death in the Longitudinal Assessment of Bariatric Surgery

Factors Related to Weight Loss up to 4 Years after Bariatric Surgery

Randomized Clinical Trial of Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Sleeve Gastrectomy for the Management of Patients with BMI < 50 kg/m2

Laparoscopic Gastric Greater Curvature Plication: Results and Complications in a Series of 135 Patients

Single-Incision Sleeve Gastrectomy Versus Conventional Laparoscopic Sleeve Gastrectomy—a Randomised Pilot Study

FTO mRNA Expression in Extremely Obese and Type 2 Diabetic Human Omental and Subcutaneous Adipose Tissues