Avaliação das vias insulínica e inflamatória em tecidos muscular esquelético e adiposo de ratos adultos, proles de ratas com lesão periapical
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Data
2019-03-29
Autores
Tsosura, Thaís Verônica Saori [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A programação fetal sugere que estímulos adversos quando aplicados durante o início do desenvolvimento fetal podem alterar o metabolismo da prole, aumentando o risco de doenças na sua vida adulta. Estudos demonstraram que a doença periodontal materna em ratas promove resistência insulínica (RI) em sua prole adulta. Entretanto, estudos que investigaram os efeitos da lesão periapical (LP) materna sobre a saúde da prole são escassos. A LP é uma inflamação no ápice da raiz dental ocasionada geralmente a partir de infecção por bactérias advindas do sistema de canal radicular. Esta patologia está associada com o aumento de fator de necrose tumoral-alfa (TNF-α) que pode estimular quinase do inibidor kappa B (IKK) e c-Jun amino-terminal quinase (JNK), as quais promovem a fosforilação do substrato do receptor de insulina 1 (IRS-1) em resíduos de serina, resultando na atenuação do sinal insulínico (SI), contribuindo com a RI. Nesse contexto, tornou-se fundamental investigar se a LP materna também promove RI em sua prole adulta. Em vista disso, os objetivos deste estudo foram avaliar os efeitos da LP materna em ratas sobre as concentrações plasmáticas de glicose, insulina e TNF-α, sensibilidade à insulina e as vias insulínica e inflamatória no músculo gastrocnêmio (MG) e tecido adiposo branco periepididimal (TABp) de sua prole adulta. Para tanto, as 15 ratas Wistar (2 meses de idade) foram distribuídas em 3 grupos: 1) ratas controle; 2) ratas com uma LP induzida em primeiro molar superior direito; 3) ratas com quatro LPs induzidas em primeiros e segundos molares superiores e inferiores do lado direito. A LP foi induzida empregando-se broca em aço carbono dotada de esfera de 0,1 mm na extremidade. Após 30 dias de exposição pulpar, as ratas de todos os grupos foram colocadas para acasalamento com ratos saudáveis. Quando os filhotes machos de todas as ratas completaram 75 dias de idade, realizaram-se os seguintes experimentos: 1) dosagem de glicemia e insulinemia, seguido pelo cálculo do Modelo de Avaliação da Homeostase da Resistência à Insulina (HOMA-IR); 2) análise da concentração plasmática de TNF-α pelo método de ensaio de imunoabsorção enzimática e 3) avaliação do grau de fosforilação em tirosina da pp185, do grau de fosforilação em serina do IRS-1 e do grau de fosforilação de IKKα/β e JNK no MG e TABp pelo método de Western blotting. A análise estatística foi feita por análise de variância, seguida pelo teste de Tukey (p<0,05). Os resultados demonstraram que a LP materna promove em sua prole adulta: 1) RI; 2) prejuízo na transdução da etapa inicial do SI no MG e TABp; 3) aumento nas concentrações plasmáticas de insulina e TNF-α; 4) maior grau de fosforilação de IKKα/β no MG e TABp; 4) inalteração na glicemia de jejum; 5) nenhuma mudança no grau de fosforilação de JNK no MG e TABp. Esses resultados demonstram que a LP materna está associada a RI e promove importantes alterações nas vias de SI e inflamação na vida adulta de sua prole. Isso reforça a importância que a manutenção da saúde bucal materna tem sobre a saúde geral da prole.
Fetal programming suggests that adverse stimuli applied during early fetal development can alter metabolism of the offspring, increasing the risk of disease in adulthood. Studies have shown that maternal periodontal disease in rats promotes insulin resistance (IR) in their adult offspring. However, there is a scarcity of research that investigated the relationship between maternal periapical lesion (PL) and health of offspring. PL is inflammatory process around the apex of a tooth root, caused by bacterial infection of the pulp and root canal system. This pathology is associated with increased tumor necrosis factor-alpha (TNF-α) which may stimulate inhibitor of kappa B kinase (IKK) and c-Jun amino-terminal kinase (JNK), which promote phosphorylation of substrate insulin receptor 1 (IRS-1) on serine residues, resulting in insulin signal (IS) attenuation, contributing to IR. In this context, it has become essential to investigate whether maternal PL also promotes IR in their offspring. This study aimed to investigate the effects of maternal PL in rats on plasma concentrations of glucose, insulin and TNF-α, insulin sensivity and the insulin and inflammatory signaling pathways in gastrocnemius muscle (GM) and periepididimal white adipose tissue (pWAT) of their adult offspring. Fifteen female Wistar rats (2 months old) were distributed in 3 groups: 1) control rats; 2) rats with 1 PL, which was induced in the right maxillary first molar; 3) rats with 4 PL, which were induced in the right upper and lower first and second molars. PL was induced using a surgical round bur 0.1 mm diameter. After 30 days of pulp exposure, female rats of all groups were mated with normal male rats. When the male offspring of rats of all rats reached 75 days old, the experiments were performed: 1) measures of glycemia and insulinemia, followed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), 2) analysis of plasma concentration of TNF-α by enzyme-linked immunosorbent assay method, and 3) evaluation of the pp185 tyrosine, IRS-1 serine, IKKα/β and JNK phosphorylation status in GM and pWAT by western blot method. Statistical analysis was performed by analysis of variance, followed by Tukey post hoc test (p<0.05). The results showed that maternal PL promotes in its adult offspring: 1) IR, 2) impairment in the transduction of the initial steps of IS in the GM and pWAT, 3) increased plasma concentrations of insulin and TNF-α, 4) greater IKKα/β phosphorylation status in GM and pWAT, 4) unchanged fasting glycemia; 5) no change in the JNK phosphorylation status in GM and pWAT. These results demonstrate that maternal PL is associated with IR and promotes important alterations in IS and inflammation pathways in adult offspring. This reinforces the importance that the maintenance of maternal oral health has on the general health of offspring.
Fetal programming suggests that adverse stimuli applied during early fetal development can alter metabolism of the offspring, increasing the risk of disease in adulthood. Studies have shown that maternal periodontal disease in rats promotes insulin resistance (IR) in their adult offspring. However, there is a scarcity of research that investigated the relationship between maternal periapical lesion (PL) and health of offspring. PL is inflammatory process around the apex of a tooth root, caused by bacterial infection of the pulp and root canal system. This pathology is associated with increased tumor necrosis factor-alpha (TNF-α) which may stimulate inhibitor of kappa B kinase (IKK) and c-Jun amino-terminal kinase (JNK), which promote phosphorylation of substrate insulin receptor 1 (IRS-1) on serine residues, resulting in insulin signal (IS) attenuation, contributing to IR. In this context, it has become essential to investigate whether maternal PL also promotes IR in their offspring. This study aimed to investigate the effects of maternal PL in rats on plasma concentrations of glucose, insulin and TNF-α, insulin sensivity and the insulin and inflammatory signaling pathways in gastrocnemius muscle (GM) and periepididimal white adipose tissue (pWAT) of their adult offspring. Fifteen female Wistar rats (2 months old) were distributed in 3 groups: 1) control rats; 2) rats with 1 PL, which was induced in the right maxillary first molar; 3) rats with 4 PL, which were induced in the right upper and lower first and second molars. PL was induced using a surgical round bur 0.1 mm diameter. After 30 days of pulp exposure, female rats of all groups were mated with normal male rats. When the male offspring of rats of all rats reached 75 days old, the experiments were performed: 1) measures of glycemia and insulinemia, followed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), 2) analysis of plasma concentration of TNF-α by enzyme-linked immunosorbent assay method, and 3) evaluation of the pp185 tyrosine, IRS-1 serine, IKKα/β and JNK phosphorylation status in GM and pWAT by western blot method. Statistical analysis was performed by analysis of variance, followed by Tukey post hoc test (p<0.05). The results showed that maternal PL promotes in its adult offspring: 1) IR, 2) impairment in the transduction of the initial steps of IS in the GM and pWAT, 3) increased plasma concentrations of insulin and TNF-α, 4) greater IKKα/β phosphorylation status in GM and pWAT, 4) unchanged fasting glycemia; 5) no change in the JNK phosphorylation status in GM and pWAT. These results demonstrate that maternal PL is associated with IR and promotes important alterations in IS and inflammation pathways in adult offspring. This reinforces the importance that the maintenance of maternal oral health has on the general health of offspring.
Descrição
Palavras-chave
Periodontite periapical, Desenvolvimento fetal, Resistência à insulina, Inflamação, Periapical periodontitis, Fetal development, Insulin resistance, Inflammation