nach oben

Journal of Endocrinological Investigation

Erschienen in:

01.01.2019 | Original Article

DNA methylation of genes regulating appetite and prediction of weight loss after bariatric surgery in obese individuals

verfasst von: F. Coppedè, M. Seghieri, A. Stoccoro, E. Santini, L. Giannini, C. Rossi, L. Migliore, A. Solini

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Epigenetic traits are influenced by clinical variables; interaction between DNA methylation (DNAmeth) and bariatric surgery-induced weight loss has been scarcely explored. We investigated whether DNAmeth of genes encoding for molecules/hormones regulating appetite, food intake or obesity could predict successful weight outcome following Roux-en-Y gastric bypass (RYGB).

Methods

Forty-five obese individuals with no known comorbidities were stratified accordingly to weight decrease one-year after RYGB (excess weight loss, EWL ≥ 50%: good responders, GR; EWL < 50%: worse responders, WR). DNAmeth of leptin (LEP), ghrelin (GHRL), ghrelin receptor (GHSR) and insulin-growth factor-2 (IGF2) was assessed before intervention. Single nucleotide polymorphisms of genes affecting DNAmeth, DNMT3A and DNMT3B, were also determined.

Results

At baseline, type 2 diabetes was diagnosed by OGTT in 13 patients. Post-operatively, GR (n = 23) and WR (n = 22) achieved an EWL of 67.7 ± 9.6 vs 38.2 ± 9.0%, respectively. Baseline DNAmeth did not differ between GR and WR for any tested genes, even when the analysis was restricted to subjects with no diabetes. A relationship between GHRL and LEP methylation profiles emerged (r = 0.47, p = 0.001). Searching for correlation between DNAmeth of the studied genes with demographic characteristics and baseline biochemical parameters of the studied population, we observed a correlation between IGF2 methylation and folate (r = 0.44, p = 0.003). Rs11683424 for DNMT3A and rs2424913 for DNMT3B did not correlate with DNAmeth of the studied genes.

Conclusions

In severely obese subjects, the degree of DNAmeth of some genes affecting obesity and related conditions does not work as predictor of successful response to RYGB.

Nur mit Berechtigung zugänglich

Schübeler D (2015) Function and information content of DNA methylation. Nature 517(7534):321–326. https://doi.org/10.1038/nature14192 CrossRefPubMed

Wang S, Wu W, Claret FX (2017) Mutual regulation of microRNAs and DNA methylation in human cancers. Epigenetics 12(3):187–197. https://doi.org/10.1080/15592294.2016.1273308 CrossRefPubMedPubMedCentral

Zhou P, Wu E, Alam HB, Li Y (2014) Histone cleavage as a mechanism for epigenetic regulation: current insights and perspectives. Curr Mol Med 14(9):1164–1172. https://doi.org/10.2174/1566524014666141015155630 CrossRefPubMedPubMedCentral

Hamidi T, Singh AK, Chen T (2015) Genetic alterations of DNA methylation machinery in human diseases. Epigenomics 7(2):247–265. https://doi.org/10.2217/epi.14.80 CrossRefPubMed

Baubec T, Colombo DF, Wirbelauer C, Schmidt J, Burger L, Krebs AR, Akalin A, Schübeler D (2015) Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature 520(7546):243–247. https://doi.org/10.1038/nature14176 CrossRefPubMed

Ronn T, Volkov P, Gillberg L, Kokosar M, Perfilyev A, Jacobsen AL, Jørgensen SW, Brøns C, Jansson PA, Eriksson KF, Pedersen O, Hansen T, Groop L, Stener-Victorin E, Vaag A, Nilsson E, Ling C (2015) Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood. Hum Mol Genet 24(13):3792–3813. https://doi.org/10.1093/hmg/ddv124 CrossRefPubMed

Olsson AH, Volkov P, Bacos K, Dayeh T, Hall E, Nilsson EA, Ladenvall C, Rönn T, Ling C (2014) Genome-wide associations between genetic and epigenetic variation influence mRNA expression and insulin secretion in human pancreatic islets. PLoS Genet 10(11):e1004735. https://doi.org/10.1371/journal.pgen.1004735 CrossRefPubMedPubMedCentral

Aronica L, Levine AJ, Brennan K, Mi J, Gardner C, Haile RW, Hitchins MP (2017) A systematic review of studies of DNA methylation in the context of a weight loss intervention. Epigenomics 9(5):769–787. https://doi.org/10.2217/epi-2016-0182 CrossRefPubMed

Crujeiras AB, Campion J, Díaz-Lagares A, Milagro FI, Goyenechea E, Abete I, Casanueva FF, Martínez JA (2013) Association of weight regain with specific methylation levels in the NPY and POMC promoters in leukocytes of obese men: a translational study. Regul Pept 186:1–6. https://doi.org/10.1016/j.regpep.2013.06.012 CrossRefPubMed

10.

Crujeiras AB, Carreira MC, Cabia B, Andrade S, Amil M, Casanueva FF (2015) Leptin resistance in obesity: an epigenetic landscape. Life Sci 140:57–63. https://doi.org/10.1016/j.lfs CrossRefPubMed

11.

Burger KS, Berner LA (2014) A functional neuroimaging review of obesity, appetitive hormones and ingestive behavior. Physiol Behav 136:121–127. https://doi.org/10.1016/j.physbeh.2014.04.025 CrossRefPubMedPubMedCentral

12.

Lee JH, Lin L, Xu P, Saito K, Wei Q, Meadows AG, Bongmba OY, Pradhan G, Zheng H, Xu Y, Sun Y (2016) Neuronal deletion of ghrelin receptor almost completely prevents diet-induced obesity. Diabetes 65(8):2169–2178. https://doi.org/10.2337/db15-1587 CrossRefPubMedPubMedCentral

13.

Anderson B, Switzer NJ, Almamar A, Shi X, Birch DW, Karmali S (2013) The impact of laparoscopic sleeve gastrectomy on plasma ghrelin levels: a systematic review. Obes Surg 23(9):1476–1480. https://doi.org/10.1007/s11695-013-0999-7 CrossRefPubMed

14.

Siejka A, Jankiewicz-Wika J, Kołomecki K, Cywiński J, Piestrzeniewicz K, Swiętosławski J, Stępień H, Komorowski J (2013) Long-term impact of vertical banded gastroplasty (VBG) on plasma concentration of leptin, soluble leptin receptor, ghrelin, omentin-1, obestatin, and retinol binding protein 4 (RBP4) in patients with severe obesity. Cytokine 64(2):490–493. https://doi.org/10.1016/j.cyto.2013.07.026 CrossRefPubMed

15.

Vitolo E, Santini E, Seghieri M, Giannini L, Coppedè F, Rossi C, Dardano A, Solini A (2017) Heterozygosity for the rs696217 SNP in the preproghrelin gene predicts weight loss after bariatric surgery in severely obese individuals. Obes Surg 27(4):961–967. https://doi.org/10.1007/s11695-016-2387-6 CrossRefPubMed

16.

Shetty PJ, Movva S, Pasupuleti N, Vedicherlla B, Vattam KK, Venkatasubramanian S, Ahuja YR, Hasan Q (2011) Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer. J Cancer Res Clin Oncol 137(2):339–345. https://doi.org/10.1007/s00432-010-0890-z CrossRefPubMed

17.

Nishihara R, Wang M, Qian ZR, Baba Y, Yamauchi M, Mima K, Sukawa Y, Kim SA, Inamura K, Zhang X, Wu K, Giovannucci EL, Chan AT, Fuchs CS, Ogino S, Schernhammer ES (2014) Alcohol, one-carbon nutrient intake, and risk of colorectal cancer according to tumor methylation level of IGF2 differentially methylated region. Am J Clin Nutr 100(6):1479–1488. https://doi.org/10.3945/ajcn.114.095539 CrossRefPubMedPubMedCentral

18.

St-Pierre J, Hivert MF, Perron P, Poirier P, Guay SP, Brisson D, Bouchard L (2012) IGF2 DNA methylation is a modulator of newborn’s fetal growth and development. Epigenetics 7(10):1125–1132. https://doi.org/10.4161/epi.21855 CrossRefPubMedPubMedCentral

19.

de Hollanda A, Ruiz T, Jiménez A, Flores L, Lacy A, Vidal J (2015) Patterns of weight loss response following gastric bypass and sleeve gastrectomy. Obes Surg 25(7):1177–1183. https://doi.org/10.1007/s11695-014-1512-7 CrossRefPubMed

20.

Farias G, Thieme RD, Teixeira LM, Heyde ME, Bettini SC, Radominski RB (2016) Good weight loss responders and poor weight loss responders after Roux-en-Y gastric bypass: clinical and nutritional profiles. Nutr Hosp 33(5):574. https://doi.org/10.20960/nh.574 CrossRefPubMed

21.

Wojdacz TK, Dobrovic A, Hansen LL (2008) Methylation-sensitive high-resolution melting. Nat Protoc 3(12):1903–1908. https://doi.org/10.1038/nprot.2008.191 CrossRefPubMed

22.

Li LC, Dahiya R (2002) MethPrimer: designing primers for methylation PCRs. Bioinformatics 18(11):1427–1431. https://doi.org/10.1093/bioinformatics/18.11.1427 CrossRefPubMed

23.

Murphy SK, Adigun A, Huang Z, Overcash F, Wang F, Jirtle RL, Schildkraut JM, Murtha AP, Iversen ES, Hoyo C (2012) Gender-specific methylation differences in relation to prenatal exposure to cigarette smoke. Gene 494(1):36–43. https://doi.org/10.1016/j.gene.2011.11.062 CrossRefPubMed

24.

Migheli F, Stoccoro A, Coppedè F, Wan Omar WA, Failli A, Consolini R, Seccia M, Spisni R, Miccoli P, Mathers JC, Migliore L (2013) Comparison study of MS-HRM and pyrosequencing techniques for quantification of APC and CDKN2A gene methylation. PLoS One 8(1):e52501. https://doi.org/10.1371/journal.pone.0052501 CrossRefPubMedPubMedCentral

25.

Pishva E, Drukker M, Viechtbauer W, Decoster J, Collip D, van Winkel R, Wichers M, Jacobs N, Thiery E, Derom C, Geschwind N, van den Hove D, Lataster T, Myin-Germeys I, van Os J, Rutten BP, Kenis G (2014) Epigenetic genes and emotional reactivity to daily life events: a multi-step gene-environment interaction study. PLoS One 9(6):e100935. https://doi.org/10.1371/journal.pone.0100935 CrossRefPubMedPubMedCentral

26.

Nicoletti CF, Nonino CB, de Oliveira BA, Pinhel MA, Mansego ML, Milagro FI, Zulet MA, Martinez JA (2016) DNA Methylation and hydroxymethylation levels in relation to two weight loss strategies: energy-restricted diet or bariatric surgery. Obes Surg 26(3):603–611. https://doi.org/10.1007/s11695-015-1802-8 CrossRefPubMed

27.

Guénard F, Tchernof A, Deshaies Y, Pérusse L, Biron S, Lescelleur O, Biertho L, Marceau S, Vohl MC (2014) Differential methylation in visceral adipose tissue of obese men discordant for metabolic disturbances. Physiol Genom 46(6):216–222. https://doi.org/10.1152/physiolgenomics.00160.2013 CrossRef

28.

Wang X, Cao Q, Yu L, Shi H, Xue B, Shi H (2016) Epigenetic regulation of macrophage polarization and inflammation by DNA methylation in obesity. JCI Insight 1(19):e87748. https://doi.org/10.1172/jci.insight.87748 CrossRefPubMedPubMedCentral

29.

Cordero P, Campion J, Milagro FI, Goyenechea E, Steemburgo T, Javierre BM, Martinez JA (2011) Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet. J Physiol Biochem 67(3):463–470. https://doi.org/10.1007/s13105-011-0084-4 CrossRefPubMed

30.

Allard C, Desgagné V, Patenaude J, Lacroix M, Guillemette L, Battista MC, Doyon M, Ménard J, Ardilouze JL, Perron P, Bouchard L, Hivert MF (2015) Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns. Epigenetics 10(4):342–351. https://doi.org/10.1080/15592294.2015.1029700 CrossRefPubMedPubMedCentral

31.

García-Cardona MC, Huang F, García-Vivas JM, López-Camarillo C, Del Río Navarro BE, Navarro Olivos E, Hong-Chong E, Bolaños-Jiménez F, Marchat LA (2014) DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance. Int J Obes (Lond) 38(11):1457–1465. https://doi.org/10.1038/ijo.2014.30 CrossRef

32.

Soubry A, Murphy SK, Wang F, Huang Z, Vidal AC, Fuemmeler BF, Kurtzberg J, Murtha A, Jirtle RL, Schildkraut JM, Hoyo C (2015) Newborns of obese parents have altered DNA methylation patterns at imprinted genes. Int J Obes (Lond) 39(4):650–657. https://doi.org/10.1038/ijo.2013.193 CrossRef

33.

Berglind D, Müller P, Willmer M, Sinha I, Tynelius P, Näslund E, Dahlman-Wright K, Rasmussen F (2016) Differential methylation in inflammation and type 2 diabetes genes in siblings born before and after maternal bariatric surgery. Obesity 24(1):250–261. https://doi.org/10.1002/oby.21340 CrossRefPubMed

34.

Navarro E, Funtikova AN, Fíto M, Schröder H (2017) Prenatal nutrition and the risk of adult obesity: long-term effects of nutrition on epigenetic mechanisms regulating gene expression. J Nutr Biochem 39:1–14. https://doi.org/10.1016/j.jnutbio.2016.03.012 CrossRefPubMed

35.

Li H, Li W, Liu S, Zong S, Wang W, Ren J, Li Q, Hou F, Shi Q (2016) DNMT1, DNMT3A and DNMT3B polymorphisms associated with gastric cancer risk: a systematic review and meta-analysis. EBioMedicine 13:125–131. https://doi.org/10.1016/j.ebiom.2016.10.028 CrossRefPubMedPubMedCentral

36.

Duan F, Cui S, Song C, Dai L, Zhao X, Zhang X (2015) Systematic evaluation of cancer risk associated with DNMT3B polymorphisms. J Cancer Res Clin Oncol 141:1205–1220. https://doi.org/10.1007/s00432-014-1894-x CrossRefPubMed

37.

Tang Q, Chen Y, Wu W, Ding H, Xia Y, Chen D, Wang X (2017) Idiopathic male infertility and polymorphisms in the DNA methyltransferase genes involved in epigenetic marking. Sci Rep 7:11219. https://doi.org/10.1038/s41598-017-11636-9 CrossRefPubMedPubMedCentral

38.

Coppedè F, Bosco P, Tannorella P, Romano C, Antonucci I, Stuppia L, Romano C, Migliore L (2013) DNMT3B promoter polymorphisms and maternal risk of birth of a child with Down syndrome. Hum Reprod 28:545–550. https://doi.org/10.1093/humrep/des376 CrossRefPubMed

39.

Cai TT, Zhang J, Wang X, Song RH, Qin Q, Muhali FS, Zhou JZ, Xu J, Zhang JA (2016) Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease. Endocr J 63:643–653. https://doi.org/10.1507/endocrj CrossRefPubMed

40.

Tajuddin SM, Amaral AF, Fernández AF, Rodríguez-Rodero S, Rodríguez RM, Moore LE, Tardón A, Carrato A, García-Closas M, Silverman DT, Jackson BP, García-Closas R, Cook AL, Cantor KP, Chanock S, Kogevinas M, Rothman N, Real FX, Fraga MF, Malats N, Spanish Bladder Cancer/EPICURO Study Investigators (2013) Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA. Environ Health Perspect 121:650–656. https://doi.org/10.1289/ehp.1206068 CrossRefPubMedPubMedCentral

Titel: DNA methylation of genes regulating appetite and prediction of weight loss after bariatric surgery in obese individuals
verfasst von: F. Coppedè
M. Seghieri
A. Stoccoro
E. Santini
L. Giannini
C. Rossi
L. Migliore
A. Solini
Publikationsdatum: 01.01.2019
Verlag: Springer International Publishing
Erschienen in: Journal of Endocrinological Investigation / Ausgabe 1/2019
Elektronische ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-018-0881-5

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

20.04.2024 | EAU 2024 | Kongressbericht | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

DNA methylation of genes regulating appetite and prediction of weight loss after bariatric surgery in obese individuals

Abstract

Purpose

Methods

Results

Conclusions

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

Parodontalbehandlung verbessert Prognose bei Katheterablation

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2019

Comment on: Lack of association between obesity and aggressiveness of differentiated thyroid cancer

Investigating the effect of testosterone by itself and in combination with letrozole on 1,25-dihydroxy vitamin D and FGF23 in male rats

Decreased staging of differentiated thyroid cancer in patients with chronic lymphocytic thyroiditis

Thanks to Reviewers 2018

Oxysterol species: reliable markers of oxidative stress in diabetes mellitus

Correction to: Effects of growth hormone on pregnancy rates of patients with thin endometrium

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

Parodontalbehandlung verbessert Prognose bei Katheterablation

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Update Innere Medizin