Associação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxico
Autor(a) principal: | |
---|---|
Data de Publicação: | 2012 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/4454 |
Resumo: | Obesity is a systemic low grade inflammation, that is associated to the increased production of proinflammatory molecules by adipose tissue. Besides, the adiposity elevated induces cellular apoptosis and release of a large amounts of free fatty acids from disrupted adipocyte. These molecules tend to accumulate in the liver and other body tissues like skeletal muscles causing a phenomenon known as lipotoxicity. Evidence suggests that in addition to fatty acids there are other molecules that could have a severe effect lipotoxicity. This is the case of the inflammatory cytokine interleukin 1 beta (IL-1β). The IL-1β is a major inflammatory cytokines in immunity system. Studies suggest that its continued production may act by reducing the glucose influx, and induces the free radicals production contributing to the maintenance of a state of oxidative stress. For this reason, some authors have suggested that IL-1β would be a molecule glicolipotóxic. In humans the expression of IL-1B is under strong genetic control. The single nucleotide polymorphism (SNP) of C to T at nucleotide position +3953 of the IL-1B gene appears to be functional because it has been associated with increased production of IL-1β in vivo. Therefore, the aim of this study was to analyze the association between the polymorphism +3953 IL-1B gene with obesity, the influence on glycemic control, lipid and oxidized LDL molecule (oxLDL). For this, two studies were performed. The first was a case-control study with 880 Caucasian individuals, classified to obesity (non-obese = 283, overweight = 334, obese = 263), age between 18-92 years, and genotyped to IL-1B +3953 polymorphism. It was measured the bioanthropometric variables (DBP, SBP, IBM, height, weight, waist circumference) and serum parameters of blood glucose, lipid profile. In the second study, we included 225 subjects genotyped previously and measured the oxLDL serum levels, besides bioanthropometric and lipid profile measures. In both studies the volunteers did not smoke and had no cardiovascular disease or chronic degenerative diseases that could affect results. The IL-1B polymorphism genotypes were determined by PCR-RFLP and biochemical parameters by spectrophotometry. The first study results showed that the C allele (CC and CT) had a higher frequency in the group of obese and overweight when compared to the non obese group. The odds ratio showed 1.340 (95% CI: 1.119-1.605) times more chance of the obese group being CC carriers compared to non-obese group independent of gender and age. The second study showed that TT genotype carriers presented lower levels of oxLDL than patients with other genotypes. However no significant influence was observed of this polymorphism in blood glucose levels. Multivariate analysis showed that this result is independent of sex, age, obesity and hypertension. Thus, these results support the hypothesis that IL-1β is a molecule indeed obesogenic and lipotoxicity as previously suggested from animal models studies. Key-word: obesity. Interleukin-1beta. Oxidized-LDL |
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2012-12-132012-12-132012-03-06CATTANI, Maria Fernanda Manica Rizzi. ASSOCIATION BETWEEN INTERLEUKIN-1 BETA GENE, OBESITY, LDL-OXIDADE AND ITS LIPOTOXICITY EFFECT POTENCIAL. 2012. 87 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/4454Obesity is a systemic low grade inflammation, that is associated to the increased production of proinflammatory molecules by adipose tissue. Besides, the adiposity elevated induces cellular apoptosis and release of a large amounts of free fatty acids from disrupted adipocyte. These molecules tend to accumulate in the liver and other body tissues like skeletal muscles causing a phenomenon known as lipotoxicity. Evidence suggests that in addition to fatty acids there are other molecules that could have a severe effect lipotoxicity. This is the case of the inflammatory cytokine interleukin 1 beta (IL-1β). The IL-1β is a major inflammatory cytokines in immunity system. Studies suggest that its continued production may act by reducing the glucose influx, and induces the free radicals production contributing to the maintenance of a state of oxidative stress. For this reason, some authors have suggested that IL-1β would be a molecule glicolipotóxic. In humans the expression of IL-1B is under strong genetic control. The single nucleotide polymorphism (SNP) of C to T at nucleotide position +3953 of the IL-1B gene appears to be functional because it has been associated with increased production of IL-1β in vivo. Therefore, the aim of this study was to analyze the association between the polymorphism +3953 IL-1B gene with obesity, the influence on glycemic control, lipid and oxidized LDL molecule (oxLDL). For this, two studies were performed. The first was a case-control study with 880 Caucasian individuals, classified to obesity (non-obese = 283, overweight = 334, obese = 263), age between 18-92 years, and genotyped to IL-1B +3953 polymorphism. It was measured the bioanthropometric variables (DBP, SBP, IBM, height, weight, waist circumference) and serum parameters of blood glucose, lipid profile. In the second study, we included 225 subjects genotyped previously and measured the oxLDL serum levels, besides bioanthropometric and lipid profile measures. In both studies the volunteers did not smoke and had no cardiovascular disease or chronic degenerative diseases that could affect results. The IL-1B polymorphism genotypes were determined by PCR-RFLP and biochemical parameters by spectrophotometry. The first study results showed that the C allele (CC and CT) had a higher frequency in the group of obese and overweight when compared to the non obese group. The odds ratio showed 1.340 (95% CI: 1.119-1.605) times more chance of the obese group being CC carriers compared to non-obese group independent of gender and age. The second study showed that TT genotype carriers presented lower levels of oxLDL than patients with other genotypes. However no significant influence was observed of this polymorphism in blood glucose levels. Multivariate analysis showed that this result is independent of sex, age, obesity and hypertension. Thus, these results support the hypothesis that IL-1β is a molecule indeed obesogenic and lipotoxicity as previously suggested from animal models studies. Key-word: obesity. Interleukin-1beta. Oxidized-LDLA obesidade é um inflamação sistêmica de baixo grau associado a elevada liberação de moléculas pró-inflamatórias pelo tecido adiposo. O aumento da adiposidade resulta em necrose tecidual e liberação de ácidos graxos, a partir dos adipócitos, que tendem a se acumular em outros tecidos corporais causando um fenômeno conhecido como lipotoxicidade. A IL-1β é uma das principais citocinas pró-inflamatórias do sistema imune, e a sua produção continuada pode agir diminuindo o influxo da glicose para dentro da célula, e induzir a produção de radicais livres contribuindo para a manutenção de um estado de estresse oxidativo. Por este motivo, alguns autores sugeriram que a IL- 1β seria uma molécula glicolipotóxica. Nos seres humanos a IL-1β possui um polimorfismo +3953 do gene da IL-1B parece ser funcional pois tem sido associado a variações na produção da IL-1β in vivo. Portanto, o objetivo deste estudo foi o de analisar a associação entre o polimorfismo +3953 do gene da IL-1B com a obesidade, a influencia nos níveis glicêmicos, lipídicos e da molécula de LDL- oxidado (LDL-ox). Para isso, foram realizados dois estudos. O primeiro foi um estudo caso-controle com 880 indivíduos Caucasianos classificados para obesidade (não obesos= 283, sobrepeso=334, obesos= 263), com idade entre 18 e 92 anos, genotipados para IL-1B +3953 determinados por PCR-RFLP. As variáveis PAD, PAS, circunferência abdominal, IMC, altura, peso, bem como o perfil glicêmico e lipídico foram medidos. No segundo estudo foram selecionados 225 indivíduos, previamente genotipados para IL-1B +3953, e medido os níveis séricos de LDL-ox, além das medidas bioantropométricas e perfil glicêmico e lipídico. Em ambos os estudos os voluntários não fumavam e não apresentavam doenças cardiovasculares ou crônico-degenerativas que pudessem interferir nos resultados. Os resultados, do primeiro estudo, mostraram que o alelo C (CT CC) apresentou uma frequência maior no grupo dos obesos e sobrepeso quando comparado ao grupo dos não obesos. A chance dos indivíduos obesos de serem portadores do genótipo CC foi de 1,34 (IC 95%, 1,119- 1,605). Estes resultados foram independente do gênero e idade. O segundo estudo mostrou que indivíduos com o genótipo CC e CT apresentaram níveis mais elevados de LDL-ox do que os portadores do genótipo TT. A análise multivariada mostrou que este resultado é independente do gênero, idade e obesidade. Entretanto, em ambos os estudos, não foi observada influência deste polimorfismo nos níveis glicêmicos. Assim, podemos concluir que a IL-1β é uma molécula, com efeito obesogênico e lipotóxico, corroborando estudos prévios em modelos animais.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaObesidadeInterleucina - 1betaLDLoxidadoObesityInterleukin-1betaOxidized-LDLCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAssociação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxicoAssociation between interleukin-1 beta gene, obesity, LDL-oxidade and its lipotoxicity effect potencialinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisCruz, Ivana Beatrice Mânica dahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4790333D6Moresco, Rafael Noalhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4765801Z9Soares, Félix Alexandre Antuneshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769181A8Schetinger, Maria Rosa ChitolinaFachinetto, Roseleihttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2http://lattes.cnpq.br/2021420099611838Cattani, Maria Fernanda Manica Rizzi2008000000024005003003005005005000b5fcfe0-b017-4163-80e2-17c110fbcf01b11c7855-63d1-4b2a-81c8-35a81348e84a05b536c5-19fb-4cae-9d69-46730a16ed09161311d0-e9c6-4e08-a436-85b4822199b4a5d2f3d1-0aa0-4c3b-89d3-b20a63b19b2447851031-d698-41a7-a810-90b77c6b42e8info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALCATTANI, MARIA FERANDA MANICA RIZZI.pdfTese de Doutoradoapplication/pdf1831817http://repositorio.ufsm.br/bitstream/1/4454/1/CATTANI%2c%20MARIA%20FERANDA%20MANICA%20RIZZI.pdf2e01db14389db7b18af90c818fb16a25MD51TEXTCATTANI, MARIA FERANDA MANICA RIZZI.pdf.txtCATTANI, MARIA FERANDA MANICA RIZZI.pdf.txtExtracted texttext/plain201007http://repositorio.ufsm.br/bitstream/1/4454/2/CATTANI%2c%20MARIA%20FERANDA%20MANICA%20RIZZI.pdf.txt56267da90334913f0bf71b9d3fbb25d5MD52THUMBNAILCATTANI, MARIA FERANDA MANICA RIZZI.pdf.jpgCATTANI, MARIA FERANDA MANICA RIZZI.pdf.jpgIM Thumbnailimage/jpeg3283http://repositorio.ufsm.br/bitstream/1/4454/3/CATTANI%2c%20MARIA%20FERANDA%20MANICA%20RIZZI.pdf.jpg227071575694fc1c94ed8f32d4b31b39MD531/44542017-08-28 16:51:13.06oai:repositorio.ufsm.br:1/4454Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-08-28T19:51:13Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Associação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxico |
dc.title.alternative.eng.fl_str_mv |
Association between interleukin-1 beta gene, obesity, LDL-oxidade and its lipotoxicity effect potencial |
title |
Associação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxico |
spellingShingle |
Associação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxico Cattani, Maria Fernanda Manica Rizzi Obesidade Interleucina - 1beta LDLoxidado Obesity Interleukin-1beta Oxidized-LDL CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Associação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxico |
title_full |
Associação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxico |
title_fullStr |
Associação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxico |
title_full_unstemmed |
Associação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxico |
title_sort |
Associação entre o polimorfismo +3954 do gene da interleucina-1 beta, obesidade, LDL-oxidado e seu potencial efeito lipotóxico |
author |
Cattani, Maria Fernanda Manica Rizzi |
author_facet |
Cattani, Maria Fernanda Manica Rizzi |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Cruz, Ivana Beatrice Mânica da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4790333D6 |
dc.contributor.referee1.fl_str_mv |
Moresco, Rafael Noal |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4765801Z9 |
dc.contributor.referee2.fl_str_mv |
Soares, Félix Alexandre Antunes |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769181A8 |
dc.contributor.referee3.fl_str_mv |
Schetinger, Maria Rosa Chitolina |
dc.contributor.referee4.fl_str_mv |
Fachinetto, Roselei |
dc.contributor.referee4Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2021420099611838 |
dc.contributor.author.fl_str_mv |
Cattani, Maria Fernanda Manica Rizzi |
contributor_str_mv |
Cruz, Ivana Beatrice Mânica da Moresco, Rafael Noal Soares, Félix Alexandre Antunes Schetinger, Maria Rosa Chitolina Fachinetto, Roselei |
dc.subject.por.fl_str_mv |
Obesidade Interleucina - 1beta LDLoxidado |
topic |
Obesidade Interleucina - 1beta LDLoxidado Obesity Interleukin-1beta Oxidized-LDL CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Obesity Interleukin-1beta Oxidized-LDL |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Obesity is a systemic low grade inflammation, that is associated to the increased production of proinflammatory molecules by adipose tissue. Besides, the adiposity elevated induces cellular apoptosis and release of a large amounts of free fatty acids from disrupted adipocyte. These molecules tend to accumulate in the liver and other body tissues like skeletal muscles causing a phenomenon known as lipotoxicity. Evidence suggests that in addition to fatty acids there are other molecules that could have a severe effect lipotoxicity. This is the case of the inflammatory cytokine interleukin 1 beta (IL-1β). The IL-1β is a major inflammatory cytokines in immunity system. Studies suggest that its continued production may act by reducing the glucose influx, and induces the free radicals production contributing to the maintenance of a state of oxidative stress. For this reason, some authors have suggested that IL-1β would be a molecule glicolipotóxic. In humans the expression of IL-1B is under strong genetic control. The single nucleotide polymorphism (SNP) of C to T at nucleotide position +3953 of the IL-1B gene appears to be functional because it has been associated with increased production of IL-1β in vivo. Therefore, the aim of this study was to analyze the association between the polymorphism +3953 IL-1B gene with obesity, the influence on glycemic control, lipid and oxidized LDL molecule (oxLDL). For this, two studies were performed. The first was a case-control study with 880 Caucasian individuals, classified to obesity (non-obese = 283, overweight = 334, obese = 263), age between 18-92 years, and genotyped to IL-1B +3953 polymorphism. It was measured the bioanthropometric variables (DBP, SBP, IBM, height, weight, waist circumference) and serum parameters of blood glucose, lipid profile. In the second study, we included 225 subjects genotyped previously and measured the oxLDL serum levels, besides bioanthropometric and lipid profile measures. In both studies the volunteers did not smoke and had no cardiovascular disease or chronic degenerative diseases that could affect results. The IL-1B polymorphism genotypes were determined by PCR-RFLP and biochemical parameters by spectrophotometry. The first study results showed that the C allele (CC and CT) had a higher frequency in the group of obese and overweight when compared to the non obese group. The odds ratio showed 1.340 (95% CI: 1.119-1.605) times more chance of the obese group being CC carriers compared to non-obese group independent of gender and age. The second study showed that TT genotype carriers presented lower levels of oxLDL than patients with other genotypes. However no significant influence was observed of this polymorphism in blood glucose levels. Multivariate analysis showed that this result is independent of sex, age, obesity and hypertension. Thus, these results support the hypothesis that IL-1β is a molecule indeed obesogenic and lipotoxicity as previously suggested from animal models studies. Key-word: obesity. Interleukin-1beta. Oxidized-LDL |
publishDate |
2012 |
dc.date.accessioned.fl_str_mv |
2012-12-13 |
dc.date.available.fl_str_mv |
2012-12-13 |
dc.date.issued.fl_str_mv |
2012-03-06 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
CATTANI, Maria Fernanda Manica Rizzi. ASSOCIATION BETWEEN INTERLEUKIN-1 BETA GENE, OBESITY, LDL-OXIDADE AND ITS LIPOTOXICITY EFFECT POTENCIAL. 2012. 87 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/4454 |
identifier_str_mv |
CATTANI, Maria Fernanda Manica Rizzi. ASSOCIATION BETWEEN INTERLEUKIN-1 BETA GENE, OBESITY, LDL-OXIDADE AND ITS LIPOTOXICITY EFFECT POTENCIAL. 2012. 87 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
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http://repositorio.ufsm.br/handle/1/4454 |
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UFSM |
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