Análise do perfil metabólico de camundongos tratados com crotamina por via oral
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Data
2016-10-31
Autores
Marinovic, Marcelo Paradiso [UNIFESP]
Orientadores
Hayashi, Mirian Akemi Furuie [UNIFESP]
Tipo
Dissertação de mestrado
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Resumo
A crotamina tem sido amplamente estudada nos últimos anos, e diversas propriedades e atividades biológicas já foram descritas, como por exemplo, sua capacidade de penetrar células com seletividade por células com alta taxa de divisão celular, capacidade de transportar genes, atividade antimicrobiana e antitumoral, atividade antiparasitária entre outros. O presente estudo tem como objetivo elucidar o possível papel da crotamina sobre o metabolismo em camundongos tratados por via oral, por 21 dias. Foram avaliados o ganho de peso, a ingestão calórica, o peso de depósitos adiposos e de outros tecidos, a análise de tolerância à glicose, a intolerância à insulina, o índice de decaimento de glicose, a análise do perfil lipídico e os marcadores de dano hepático e renal plasmático, o gasto energético basal, os genes termogênicos no tecido adiposo marrom (TAM) do animal tratado e em células adiposas marrons linhagem 9b tratadas em cultivo, os genes de diferenciação no tecido adiposo branco (TAB), perfil de células imunes infiltradas no TAB, além da análise do perfil da microbiota intestinal dos animais tratados. Os resultados aqui descritos sugerem que o tratamento com crotamina por via oral reduz o ganho de peso, assim como diminui os depósitos adiposos brancos. Observou-se ainda a redução da tolerância à glicose, da intolerância à insulina, dos níveis de lipídios (TG, LDL e colesterol), dos marcadores de dano hepático (GAMA-GT) e renal (ácido úrico e creatina), além de um aumento significativo do TAM e do gasto energético basal. Observamos ainda o aumento de marcadores termogênicos (UCP-1, PGC1?, PRDM16, PPAR?) no TAM dos animais tratados e também nas células 9b tratadas in vitro, além da indução da diferenciação de células adiposas brancas in vitro, evidenciada pelo aumento da expressão de PRDM16 e UCP-1, alem do aumento da ocorrência de macrófagos M2 infiltrados no TAB. Foi observado também a alteração no perfil da microbiota intestinal, com aumento de firmicutes e diminuição de bacterioidetes. Diante disto, concluímos que o tratamento com a crotamina diminui o ganho de peso dos animais devido a um aumento do gasto energético promovido pelo aumento das vias termogênicas tanto em células adiposas marrons como brancas.
Crotamine has been extensively studied in the last few years, and several properties and biological activities have been described, for instance, crotamine‟s ability to penetrate cells with selectivity for those with high rate of cell division, to carry genes, in addition to antimicrobial and antitumor activities, antiparasitic activity among others. The present study aimed to elucidate the possible effects of crotamine on metabolism in mice treated orally with crotamine, during 21 days. The weight gain, caloric intake, the weight of fatty deposits and other tissues, analysis of glucose tolerance, intolerance to insulin, glucose decay rate, the lipid profile and serum markers of liver and kidney damage, basal energy expenditure, thermogenic genes in brown adipose tissue (BAT) and in brown fat cells line 9b, differentiation genes in white adipose tissue (WAT), immune cells markers in the WAT, and the analysis of profile of the intestinal tract of treated animals. The results described here suggest that treatment with crotamine orally reduces weight gain as well as decreases the white adipose deposits. It was also observed reduced glucose tolerance, intolerance to insulin, change in lipid levels (TG, LDL and cholesterol), the liver damage markers (gamma GT) and kidney (uric acid and creatine acid), and a significant increase of TAM and basal energy expenditure. We also observed the increase in thermogenic markers (namely UCP1, PGC1α, PRDM16, PPARα) in TAM of animals treated with crotamine by oral route and also in 9b cells treated with crotaminein vitro, in addition to the differentiation of white adipose cells induced by crotaminein vivo, as evidenced by the augmented expression of PRDM16 and UCP1 in these cells and the increase in M2 macrophages infiltration in this tissue.Change in the compostionof the intestinal microbiota, with increased firmicutes and decreased bacterioidetes, was also observed. Taken together, we show here that the treatment with crotamine reduces the weight gain of the animals due to an increase in energy expenditure promoted by increased thermogenic pathways in both adipose cells, brown and white tissues.
Crotamine has been extensively studied in the last few years, and several properties and biological activities have been described, for instance, crotamine‟s ability to penetrate cells with selectivity for those with high rate of cell division, to carry genes, in addition to antimicrobial and antitumor activities, antiparasitic activity among others. The present study aimed to elucidate the possible effects of crotamine on metabolism in mice treated orally with crotamine, during 21 days. The weight gain, caloric intake, the weight of fatty deposits and other tissues, analysis of glucose tolerance, intolerance to insulin, glucose decay rate, the lipid profile and serum markers of liver and kidney damage, basal energy expenditure, thermogenic genes in brown adipose tissue (BAT) and in brown fat cells line 9b, differentiation genes in white adipose tissue (WAT), immune cells markers in the WAT, and the analysis of profile of the intestinal tract of treated animals. The results described here suggest that treatment with crotamine orally reduces weight gain as well as decreases the white adipose deposits. It was also observed reduced glucose tolerance, intolerance to insulin, change in lipid levels (TG, LDL and cholesterol), the liver damage markers (gamma GT) and kidney (uric acid and creatine acid), and a significant increase of TAM and basal energy expenditure. We also observed the increase in thermogenic markers (namely UCP1, PGC1α, PRDM16, PPARα) in TAM of animals treated with crotamine by oral route and also in 9b cells treated with crotaminein vitro, in addition to the differentiation of white adipose cells induced by crotaminein vivo, as evidenced by the augmented expression of PRDM16 and UCP1 in these cells and the increase in M2 macrophages infiltration in this tissue.Change in the compostionof the intestinal microbiota, with increased firmicutes and decreased bacterioidetes, was also observed. Taken together, we show here that the treatment with crotamine reduces the weight gain of the animals due to an increase in energy expenditure promoted by increased thermogenic pathways in both adipose cells, brown and white tissues.
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Citação
MARINOVIC, Marcelo Paradiso. Análise do perfil metabólico de camundongos tratados com crotamina por via oral. 2016. 93 f. Dissertação (Mestrado em Farmacologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2016.