Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito

Detalhes bibliográficos
Autor(a) principal: Nobre, Jessica Lopes
Data de Publicação: 2015
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
Texto Completo: http://www.bdtd.uerj.br/handle/1/12663
Resumo: Obesity is a worldwide epidemic and in Brazil more than 50% of people are overweight/obese. We show that a rich calcium diet has an anti-obesity effect in obese animals programmed by early weaning (EW), an effect mediated by vitamin D action, which appears to directly regulate adipogenesis. Thus, we decided to evaluate the effect of vitamin D on the metabolism of adipose tissue in vivo with EW animals and in vitro with 3T3L1 lineage. At birth, lactating rats were divided into: EW Group, dams were wrapped with a bandage to interrupt lactation in the last 3 days of lactation; C Group, dams whose pups had free access to breast milk during the lactation period (21 days). At 120 days-old, EW offspring were subdivided into: EW standard diet; EW, received calcium supplementation (EWCa, calcium carbonate 10g / kg chow). We also use 3T3L1 cell line to incubated with calcitriol (1,25 (OH) 2D) or leptin. Significance level was at p<0,05. Ew offspring had lower body weight during the 3 days of weaning and lower ionized calcium, without changing in plasma calcidiol (25(OH)D). At 120 days-old (first day of calcium diet) there was no difference in body weight, food intake, body total fat and visceral fat. At 180 days-old, the EW animals were overweight, hyperphagia, higher total and visceral body fat, increased adipocyte area, higher leptin content in visceral adipose tissue, lower content of OBRb and SOCS3. There was an increase in serum levels of 25(OH)D, no change in 1,25(OH)2D levels and PTH. In liver, the EW animals had no change in Cyp2r1, SIRT1 and cholesterol, but showed lower VDR and PPARα, and increased triglyceride content. In kidney of the animals, had no difference in VDR expression, Cyp27b1/1α-Hydroxylase and Cyp24/24hydroxylase. In the gut, there was a lower calbindin and no change in VDR. In adipose tissue, EW animals had lower VDR expression and higher Cyp27b1/1α-hydroxylase expression, C/EBP-β, PPARg, IL-6, MCP1 and TNFα, and no change in IL1β and lower IL10. We observed no change in plasma inflammatory cytokines. We found higher TBARS and carbonyl in liver. The calcium supplemented diet normalized almost all disorders found in EW group. In 3T3L1 cells, 1,25(OH)2D incubation decreased CYP27B1/1α-hydroxylase and VDR expression, and despite higher VDR content; decreased cell proliferation with no change in apoptosis. The leptin incubation decreased CYP27B1/1α-hydroxylase; and the co-incubation decreased VDR expression with no change in CYP27B1/1α-hydroxylase. Early weaning leads to malnutrition and hypocalcemia, reflecting on changes in vitamin D metabolism/action, contributing to long-term to vitamin D resistance and higher adiposity, inflammation and oxidative stress. Dietary calcium supplementation during 2 months protect against the development of these disorders en EW group.
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spelling Oliveira, Elaine dehttp://lattes.cnpq.br/7322797152004960Moura, Egberto Gaspar dehttp://lattes.cnpq.br/9398848717949756Silva, Patrícia Cristina Lisbôa dahttp://lattes.cnpq.br/6704904748735082Daleprane, Júlio Beltramehttp://lattes.cnpq.br/6027048461430935Ortiga, Tania Maria Ruffonihttp://lattes.cnpq.br/4392742123368877Bressan, Josefinahttp://lattes.cnpq.br/6723886773861125http://lattes.cnpq.br/6030654872620366Nobre, Jessica Lopes2021-01-06T20:54:11Z2016-11-032015-09-30NOBRE, Jessica Lopes. Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito. 2015. 91 f. Tese (Doutorado em Fisiopatologia Clínica e Experimental) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2015.http://www.bdtd.uerj.br/handle/1/12663Obesity is a worldwide epidemic and in Brazil more than 50% of people are overweight/obese. We show that a rich calcium diet has an anti-obesity effect in obese animals programmed by early weaning (EW), an effect mediated by vitamin D action, which appears to directly regulate adipogenesis. Thus, we decided to evaluate the effect of vitamin D on the metabolism of adipose tissue in vivo with EW animals and in vitro with 3T3L1 lineage. At birth, lactating rats were divided into: EW Group, dams were wrapped with a bandage to interrupt lactation in the last 3 days of lactation; C Group, dams whose pups had free access to breast milk during the lactation period (21 days). At 120 days-old, EW offspring were subdivided into: EW standard diet; EW, received calcium supplementation (EWCa, calcium carbonate 10g / kg chow). We also use 3T3L1 cell line to incubated with calcitriol (1,25 (OH) 2D) or leptin. Significance level was at p<0,05. Ew offspring had lower body weight during the 3 days of weaning and lower ionized calcium, without changing in plasma calcidiol (25(OH)D). At 120 days-old (first day of calcium diet) there was no difference in body weight, food intake, body total fat and visceral fat. At 180 days-old, the EW animals were overweight, hyperphagia, higher total and visceral body fat, increased adipocyte area, higher leptin content in visceral adipose tissue, lower content of OBRb and SOCS3. There was an increase in serum levels of 25(OH)D, no change in 1,25(OH)2D levels and PTH. In liver, the EW animals had no change in Cyp2r1, SIRT1 and cholesterol, but showed lower VDR and PPARα, and increased triglyceride content. In kidney of the animals, had no difference in VDR expression, Cyp27b1/1α-Hydroxylase and Cyp24/24hydroxylase. In the gut, there was a lower calbindin and no change in VDR. In adipose tissue, EW animals had lower VDR expression and higher Cyp27b1/1α-hydroxylase expression, C/EBP-β, PPARg, IL-6, MCP1 and TNFα, and no change in IL1β and lower IL10. We observed no change in plasma inflammatory cytokines. We found higher TBARS and carbonyl in liver. The calcium supplemented diet normalized almost all disorders found in EW group. In 3T3L1 cells, 1,25(OH)2D incubation decreased CYP27B1/1α-hydroxylase and VDR expression, and despite higher VDR content; decreased cell proliferation with no change in apoptosis. The leptin incubation decreased CYP27B1/1α-hydroxylase; and the co-incubation decreased VDR expression with no change in CYP27B1/1α-hydroxylase. Early weaning leads to malnutrition and hypocalcemia, reflecting on changes in vitamin D metabolism/action, contributing to long-term to vitamin D resistance and higher adiposity, inflammation and oxidative stress. Dietary calcium supplementation during 2 months protect against the development of these disorders en EW group.A obesidade é uma epidemia mundial e no Brasil mais de 50% dos indivíduos se encontram com sobrepeso/obesidade. Demonstramos que uma dieta rica em cálcio apresenta um efeito anti-obesidade em animais obesos programados pelo desmame precoce (DP), efeito este mediado pela ação da vitamina D, que parece regular diretamente a adipogênese. Assim, decidimos avaliar o efeito da vitamina D sobre o metabolismo do tecido adiposo em experimentos in vivo com animais DP e em um sistema in vitro com linhagem 3T3L1. Ao nascimento de suas proles, as lactantes foram divididas em: Grupo DP, ratas envolvidas em atadura para interromper o acesso dos filhotes ao leite materno nos 3 últimos dias da lactação; Grupo C, mães controles cujos filhotes tiveram livre acesso ao leite materno durante o período padrão de lactação (21 dias). Aos 120 dias de idade, as proles do grupo DP foram subdivididas em: DP dieta padrão; DP suplementado com cálcio (DPCa, 10g de carbonato de cálcio/kg de ração). Ainda utilizamos linhagem de células 3T3L1 incubadas com calcitriol (1.25(OH)2D) ou leptina. As proles do grupo DP apresentaram menor peso corporal durante os 3 dias do desmame e menor cálcio ionizado, sem alteração de calcidiol (25(OH)D) plasmático. Aos 120 dias (início da suplementação com cálcio) não houve diferença na massa corporal, ingestão alimentar, percentual de gordura total e de gordura do visceral. Já aos 180 dias, a prole DP apresentou sobrepeso, hiperfagia, maior adiposidade corporal total e visceral, aumento da área do adipócito, maior conteúdo de leptina no tecido adiposo visceral, menor conteúdo do ObRb e da SOCS3. Houve um aumento nas concentrações plasmáticas de 25(OH)D, sem alteração nos níveis de 1.25(OH)2D e PTH. No fígado, os animais DP não diferiram quanto Cyp2r1, sirtuína1 e colesterol, mas apresentaram menor VDR e PPARα, e maior conteúdo de triglicerídeo. No rim, esses animais não alteraram a expressão de VDR, Cyp27b1/1α-hidroxilase ou Cyp24/24hidroxilase. No intestino, houve diminuição da calbindina, sem alteração do VDR. No tecido adiposo (TA), menor expressão do VDR e maior expressão de Cyp27b1/1α-hidroxilase, C/EBP-β e PPARg, bem como aumento de IL6, MCP1, TNFα, sem alterar IL1b e menor IL10. A dieta rica em cálcio normalizou quase todas desordens encontradas no grupo DP. Nas células 3T3L1, a incubação com 1.25(OH)2D diminuiu a expressão de Cyp27b1/1α-hidroxilase e VDR, apesar de aumentar o conteúdo do VDR; diminuiu a proliferação sem alterar apoptose. A incubação com leptina diminuiu a Cyp27b1/1α-hidroxilase; e a co-incubação diminuiu a expressão do VDR sem alterar a Cyp27b1/1α-hidroxilase. O DP tem efeito imediato causando desnutrição e hipocalcemia, repercutindo em modificações no metabolismo/ação da vitamina D, contribuindo em longo prazo para resistência a este hormônio e maior adiposidade, inflamação e estresse oxidativo, prevenidos pela suplementação por dois meses com cálcio dietético.Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:54:11Z No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Jessica_Lopes_nobre.pdf: 1744205 bytes, checksum: 37b25eb634ba1d2a2639627f2f57a89f (MD5)Made available in DSpace on 2021-01-06T20:54:11Z (GMT). No. of bitstreams: 1 TESE_FINAL_PUBLICADA_Jessica_Lopes_nobre.pdf: 1744205 bytes, checksum: 37b25eb634ba1d2a2639627f2f57a89f (MD5) Previous issue date: 2015-09-30Fundação de Amparo à Pesquisa do Estado do Rio de Janeiroapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em Fisiopatologia Clínica e ExperimentalUERJBRCentro Biomédico::Faculdade de Ciências MédicasEarly weaningProgrammingObesityCalcium dietVitamin DDesmame precoceProgramaçãoObesidadeCálcioVitamina DObesidadeAdipócitosCálcio Efeito fisiológicoDesmameVitamina DCNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA ENDOCRINATerapia antiobesidade com cálcio papel da ação da vitamina D no adipócitoCalcium anti-obesity therapy: role of vitamin D in the adipocyteinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALTESE_FINAL_PUBLICADA_Jessica_Lopes_nobre.pdfapplication/pdf1744205http://www.bdtd.uerj.br/bitstream/1/12663/1/TESE_FINAL_PUBLICADA_Jessica_Lopes_nobre.pdf37b25eb634ba1d2a2639627f2f57a89fMD511/126632024-02-26 16:36:37.427oai:www.bdtd.uerj.br:1/12663Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T19:36:37Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false
dc.title.por.fl_str_mv Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito
dc.title.alternative.eng.fl_str_mv Calcium anti-obesity therapy: role of vitamin D in the adipocyte
title Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito
spellingShingle Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito
Nobre, Jessica Lopes
Early weaning
Programming
Obesity
Calcium diet
Vitamin D
Desmame precoce
Programação
Obesidade
Cálcio
Vitamina D
Obesidade
Adipócitos
Cálcio Efeito fisiológico
Desmame
Vitamina D
CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA ENDOCRINA
title_short Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito
title_full Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito
title_fullStr Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito
title_full_unstemmed Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito
title_sort Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito
author Nobre, Jessica Lopes
author_facet Nobre, Jessica Lopes
author_role author
dc.contributor.advisor1.fl_str_mv Oliveira, Elaine de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/7322797152004960
dc.contributor.advisor-co1.fl_str_mv Moura, Egberto Gaspar de
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/9398848717949756
dc.contributor.referee1.fl_str_mv Silva, Patrícia Cristina Lisbôa da
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/6704904748735082
dc.contributor.referee2.fl_str_mv Daleprane, Júlio Beltrame
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/6027048461430935
dc.contributor.referee3.fl_str_mv Ortiga, Tania Maria Ruffoni
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/4392742123368877
dc.contributor.referee4.fl_str_mv Bressan, Josefina
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/6723886773861125
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6030654872620366
dc.contributor.author.fl_str_mv Nobre, Jessica Lopes
contributor_str_mv Oliveira, Elaine de
Moura, Egberto Gaspar de
Silva, Patrícia Cristina Lisbôa da
Daleprane, Júlio Beltrame
Ortiga, Tania Maria Ruffoni
Bressan, Josefina
dc.subject.eng.fl_str_mv Early weaning
Programming
Obesity
Calcium diet
Vitamin D
topic Early weaning
Programming
Obesity
Calcium diet
Vitamin D
Desmame precoce
Programação
Obesidade
Cálcio
Vitamina D
Obesidade
Adipócitos
Cálcio Efeito fisiológico
Desmame
Vitamina D
CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA ENDOCRINA
dc.subject.por.fl_str_mv Desmame precoce
Programação
Obesidade
Cálcio
Vitamina D
Obesidade
Adipócitos
Cálcio Efeito fisiológico
Desmame
Vitamina D
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA ENDOCRINA
description Obesity is a worldwide epidemic and in Brazil more than 50% of people are overweight/obese. We show that a rich calcium diet has an anti-obesity effect in obese animals programmed by early weaning (EW), an effect mediated by vitamin D action, which appears to directly regulate adipogenesis. Thus, we decided to evaluate the effect of vitamin D on the metabolism of adipose tissue in vivo with EW animals and in vitro with 3T3L1 lineage. At birth, lactating rats were divided into: EW Group, dams were wrapped with a bandage to interrupt lactation in the last 3 days of lactation; C Group, dams whose pups had free access to breast milk during the lactation period (21 days). At 120 days-old, EW offspring were subdivided into: EW standard diet; EW, received calcium supplementation (EWCa, calcium carbonate 10g / kg chow). We also use 3T3L1 cell line to incubated with calcitriol (1,25 (OH) 2D) or leptin. Significance level was at p<0,05. Ew offspring had lower body weight during the 3 days of weaning and lower ionized calcium, without changing in plasma calcidiol (25(OH)D). At 120 days-old (first day of calcium diet) there was no difference in body weight, food intake, body total fat and visceral fat. At 180 days-old, the EW animals were overweight, hyperphagia, higher total and visceral body fat, increased adipocyte area, higher leptin content in visceral adipose tissue, lower content of OBRb and SOCS3. There was an increase in serum levels of 25(OH)D, no change in 1,25(OH)2D levels and PTH. In liver, the EW animals had no change in Cyp2r1, SIRT1 and cholesterol, but showed lower VDR and PPARα, and increased triglyceride content. In kidney of the animals, had no difference in VDR expression, Cyp27b1/1α-Hydroxylase and Cyp24/24hydroxylase. In the gut, there was a lower calbindin and no change in VDR. In adipose tissue, EW animals had lower VDR expression and higher Cyp27b1/1α-hydroxylase expression, C/EBP-β, PPARg, IL-6, MCP1 and TNFα, and no change in IL1β and lower IL10. We observed no change in plasma inflammatory cytokines. We found higher TBARS and carbonyl in liver. The calcium supplemented diet normalized almost all disorders found in EW group. In 3T3L1 cells, 1,25(OH)2D incubation decreased CYP27B1/1α-hydroxylase and VDR expression, and despite higher VDR content; decreased cell proliferation with no change in apoptosis. The leptin incubation decreased CYP27B1/1α-hydroxylase; and the co-incubation decreased VDR expression with no change in CYP27B1/1α-hydroxylase. Early weaning leads to malnutrition and hypocalcemia, reflecting on changes in vitamin D metabolism/action, contributing to long-term to vitamin D resistance and higher adiposity, inflammation and oxidative stress. Dietary calcium supplementation during 2 months protect against the development of these disorders en EW group.
publishDate 2015
dc.date.issued.fl_str_mv 2015-09-30
dc.date.available.fl_str_mv 2016-11-03
dc.date.accessioned.fl_str_mv 2021-01-06T20:54:11Z
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dc.identifier.citation.fl_str_mv NOBRE, Jessica Lopes. Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito. 2015. 91 f. Tese (Doutorado em Fisiopatologia Clínica e Experimental) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2015.
dc.identifier.uri.fl_str_mv http://www.bdtd.uerj.br/handle/1/12663
identifier_str_mv NOBRE, Jessica Lopes. Terapia antiobesidade com cálcio papel da ação da vitamina D no adipócito. 2015. 91 f. Tese (Doutorado em Fisiopatologia Clínica e Experimental) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2015.
url http://www.bdtd.uerj.br/handle/1/12663
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dc.publisher.none.fl_str_mv Universidade do Estado do Rio de Janeiro
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dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Centro Biomédico::Faculdade de Ciências Médicas
publisher.none.fl_str_mv Universidade do Estado do Rio de Janeiro
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