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O papel de trib2 no metabolismo celular: análise dos níveis de expressão de trib2 em tecidos metabolicamente ativos
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Advisor(s)
Abstract(s)
A resistência à insulina é um fator chave na patogénese da síndrome metabólica e na
diabetes mellitus tipo 2 (DM2), potenciando outros problemas de saúde, tal como o aumento
do risco para alguns tipos de cancro.
TRIB2 é um dos três membros da família Tribbles de proteínas pseudoquinases. Em vez
da fosforilação direta das proteínas alvo, atuam como adaptadores nas vias de sinalização de
importantes processos celulares. TRIB2 interage e ativa a proteína AKT associada à supressão
da FOXO e dos seus genes alvo. Os fatores de transcrição FOXO são os principais alvos da
ação da insulina e a sua desregulação promove o desenvolvimento de diabetes. A via de
sinalização PI3K/AKT é uma das mais frequentemente ativadas no cancro, pois a hiperativação
de AKT está associada ao aumento da proliferação celular e metabolismo de energia celular.
Assim, surgiu a hipótese que TRIB2 pode desempenhar um papel crucial no metabolismo
celular.
Este trabalho teve o objetivo de avaliar os níveis de expressão de TRIB2 em determinados
tecidos metabólicos (fígado, músculo esquelético e tecidos adiposos branco (WAT) e castanho
(BAT)) em resposta a condições específicas (obesidade, DM2, resistência à insulina, exposição
ao frio, tratamento com rosiglitazona) em amostras de tecidos de humanos e de origem murina,
utilizando a base de dados GEO (NCBI). Foi também avaliada quantitativamente a expressão
génica de TRIB2 no tecido adiposo de ratinhos magros e obesos, através da realização de reação
em cadeia da polimerase (PCR) em tempo real.
Na análise GEO verificou-se no fígado uma diminuição da expressão de TRIB2 na
obesidade, enquanto que no WAT ocorreu um aumento na mesma condição. Além disso, a sua
expressão no WAT diminuiu em resposta ao tratamento com rosiglitazona. No músculo
esquelético não se encontraram diferenças significativas na sua expressão na obesidade, DM2
ou resistência à insulina. Ao comparar o BAT e WAT, verificou-se uma expressão preferencial
de TRIB2 no WAT. TRIB2 aumentou, no BAT, em resposta ao frio.
Na análise quantitativa de TRIB2 no WAT, não foi possível observar alteração
estatisticamente significativa na sua expressão dependente da obesidade induzida pela dieta rica
em gorduras.
Insulin resistance is a key factor in the pathogenesis of the metabolic syndrome and in type 2 diabetes, potentiating other health problems, such as the increased risk for some types of cancer. TRIB2 is one of three members of the Tribbles family of pseudokinases proteins. Instead of direct phosphorylation of target proteins, they act as adapters in the signaling pathways of important cellular processes. TRIB2 interacts and activates AKT protein, associated with suppression of FOXO and its target genes. FOXO transcription factors are the main targets of the action of insulin and its deregulation promotes the development of diabetes. PI3K/AKT signaling pathway is one of the most frequently activated in cancer, as AKT hyperactivation is associated with increased cell proliferation and cellular energy metabolism. Thus, our hypothesis is that TRIB2 may play a crucial role in cellular metabolism. This study aimed to evaluate the levels of TRIB2 expression in certain metabolic tissues (liver, skeletal muscle and white and brown adipose tissues (WAT and BAT, respectively) in response to specific conditions (obesity, DM2, insulin resistance, cold exposure, treatment with rosiglitazone) in samples of human and murine tissues, using the GEO database (NCBI). The gene expression of TRIB2 in the adipose tissue of lean and obese mice was also quantitatively evaluated by performing Real-time polymerase chain reaction (PCR). In the GEO analysis there was a decrease in the expression of TRIB2 in obesity in the liver, while in WAT there was an increase in the same condition. In addition, its expression in WAT decreased in response to treatment with rosiglitazone. In skeletal muscle, no significant differences were found in its expression in obesity, DM2 or insulin resistance. When comparing BAT and WAT, there was a preferential expression of TRIB2 in WAT. TRIB2 increased in BAT, in response to the cold. In the quantitative analysis of TRIB2 in WAT, it was not possible to observe a statistically significant change in its expression dependent on obesity induced by a high-fat diet.
Insulin resistance is a key factor in the pathogenesis of the metabolic syndrome and in type 2 diabetes, potentiating other health problems, such as the increased risk for some types of cancer. TRIB2 is one of three members of the Tribbles family of pseudokinases proteins. Instead of direct phosphorylation of target proteins, they act as adapters in the signaling pathways of important cellular processes. TRIB2 interacts and activates AKT protein, associated with suppression of FOXO and its target genes. FOXO transcription factors are the main targets of the action of insulin and its deregulation promotes the development of diabetes. PI3K/AKT signaling pathway is one of the most frequently activated in cancer, as AKT hyperactivation is associated with increased cell proliferation and cellular energy metabolism. Thus, our hypothesis is that TRIB2 may play a crucial role in cellular metabolism. This study aimed to evaluate the levels of TRIB2 expression in certain metabolic tissues (liver, skeletal muscle and white and brown adipose tissues (WAT and BAT, respectively) in response to specific conditions (obesity, DM2, insulin resistance, cold exposure, treatment with rosiglitazone) in samples of human and murine tissues, using the GEO database (NCBI). The gene expression of TRIB2 in the adipose tissue of lean and obese mice was also quantitatively evaluated by performing Real-time polymerase chain reaction (PCR). In the GEO analysis there was a decrease in the expression of TRIB2 in obesity in the liver, while in WAT there was an increase in the same condition. In addition, its expression in WAT decreased in response to treatment with rosiglitazone. In skeletal muscle, no significant differences were found in its expression in obesity, DM2 or insulin resistance. When comparing BAT and WAT, there was a preferential expression of TRIB2 in WAT. TRIB2 increased in BAT, in response to the cold. In the quantitative analysis of TRIB2 in WAT, it was not possible to observe a statistically significant change in its expression dependent on obesity induced by a high-fat diet.
Description
Keywords
Obesidade Diabetes Metabolismo Tecido adiposo Tribbles TRIB2