Altered pathways in methylome and transcriptome longitudinal analysis of normal weight and bariatric surgery women

Autor(es)

Nicoletti, C. F. . ^[1] ; Pinhel, M. A. S. ^{[1, 2, 3]} ; Noronha, N. Y. ^{[1, 2]} ; de Oliveira, B. A. ^{[1, 2]} ; Salgado Junior, W. ^[4] ; Jacome, A. ^[5] ; Diaz-Lagares, A. ^{[6, 7]} ; Casanueva, F. ^{[8, 9, 1, 10]} ; Crujeiras, A. B. ^{[8, 9, 10]} ; Nonino, C. B. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Hlth Sci Dept, Lab Nutrigen Studies, Ribeirao Preto - Brazil

^[2] Crujeiras, A. B., CIBER Fisiopatol Obesidad \& Nutr CIBERobn, Madrid, Spain.Nicoletti, C. F. ., Univ Sao Paulo, Ribeirao Preto Med Sch, Hlth Sci Dept, Lab Nutrigen Studies, Ribeirao Preto - Brazil

^[3] Sao Jose do Rio Preto Med Sch, Dept Mol Biol, Lab Studies Biochem & Mol Biol, Sao Jose Do Rio Preto - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Sao Paulo - Brazil

^[5] Univ A Coruna, Fac Sci, CITIC, Dept Math, MODES Grp, La Coruna - Spain

^[6] Complejo Hosp Univ Santiago CHUS, CIBERONC, Inst Invest Sanitaria IDIS, Translat Med Oncol Oncomet, Santiago De Compostela - Spain

^[7] Univ Clin Hosp Santiago CHUS, Roche CHUS Joint Unit, Santiago De Compostela - Spain

^[8] Santiago de Compostela Univ USC, Santiago De Compostela - Spain

^[9] CIBER Fisiopatol Obesidad & Nutr CIBERobn, Madrid - Spain

^[10] Complejo Hosp Univ Santiago CHUS, Inst Invest Sanitaria IDIS, Epigen Endocrinol & Nutr, Santiago De Compostela - Spain

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 APR 15 2020.
• Citações Web of Science: 1

Resumo

DNA methylation could provide a link between environmental, genetic factors and weight control and can modify gene expression pattern. This study aimed to identify genes, which are differentially expressed and methylated depending on adiposity state by evaluating normal weight women and obese women before and after bariatric surgery (BS). We enrolled 24 normal weight (BMI: 22.5 +/- 1.6kg/m(2)) and 24 obese women (BMI: 43.3 +/- 5.7kg/m(2)) submitted to BS. Genome-wide methylation analysis was conducted using Infinium Human Methylation 450 BeadChip (threshold for significant CpG sites based on delta methylation level with a minimum value of 5%, a false discovery rate correction (FDR) of q<0.05 was applied). Expression levels were measured using HumanHT-12v4 Expression BeadChip (cutoff of p <less than or equal to> 0.05 and fold change >= 2.0 was used to detect differentially expressed probes). The integrative analysis of both array data identified four genes (i.e. TPP2, PSMG6, ARL6IP1 and FAM49B) with higher methylation and lower expression level in pre-surgery women compared to normal weight women: and two genes (i.e. ZFP36L1 and USP32) that were differentially methylated after BS. These methylation changes were in promoter region and gene body. All genes are related to MAPK cascade, NIK/NF-kappaB signaling, cellular response to insulin stimulus, proteolysis and others. Integrating analysis of DNA methylation and gene expression evidenced that there is a set of genes relevant to obesity that changed after BS. A gene ontology analysis showed that these genes were enriched in biological functions related to adipogenesis, orexigenic, oxidative stress and insulin metabolism pathways. Also, our results suggest that although methylation plays a role in gene silencing, the majority of effects were not correlated. (AU)

• Processo FAPESP: 17/07220-7 - Aplicação de ferramentas de bioinformática para análise do perfil de metilação do DNA antes e após a cirurgia bariátrica
• Beneficiário: Carolina Nicoletti Ferreira Fino
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 16/05638-1 - Padrão de metilação global do DNA antes e após tratamentos para perda de peso
• Beneficiário: Carla Barbosa Nonino
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/12819-4 - Alterações genéticas, clínicas, bioquímicas e de variabilidade cardíaca na Obesidade grau III pré e pós-cirurgia bariátrica
• Beneficiário: Marcela Augusta de Souza Pinhel
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/18669-0 - Avaliação do padrão de metilação do DNA antes e após derivação gástrica em Y-de-Roux
• Beneficiário: Carolina Nicoletti Ferreira Fino
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado