Mattera Maria Sara de Lima Coutinho, Chiba Fernando Yamamoto, Mota Max Sander de Oliveira da, Pereira Renato Felipe, Ervolino Edilson, Chaves Neto Antonio Hernandes, Salzedas Leda Maria Pescinini, Scaramele Natália Francisco, Silva Cristina Antoniali, Okamoto Maristela Mitiko, Machado Ubiratan Fabres, Sumida Doris Hissako
Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas-SBFis - Department of Basic Sciences, Dental School of Araçatuba, Univ Estadual Paulista - UNESP, Araçatuba, SP, Brazil.
Preventive and Social Dentistry Post-Graduation Program, Dental School of Araçatuba, Univ Estadual Paulista - UNESP, Brazil.
Life Sci. 2016 Mar 1;148:194-200. doi: 10.1016/j.lfs.2016.02.010. Epub 2016 Feb 23.
The fetal programming hypothesis suggests that intrauterine stimuli can induce metabolic changes in offspring, increasing the disease risk in adulthood. Periodontal disease may enhance serum cytokine levels. Cytokines such as tumor necrosis factor-alpha (TNF-α) have been associated with reduced glucose transporter type 4 (GLUT4) expression, decreased protein kinase B (Akt) phosphorylation, and insulin resistance. This study aimed to evaluate GLUT4 content, and Akt serine phosphorylation status in the gastrocnemius skeletal muscle (GSM), glycemia, insulinemia and change in body weight in offspring of rats with periodontal disease.
Female Wistar rats were distributed into a control group (CN) and an experimental periodontal disease group (PD), in which a ligature was placed around the mandibular first molars. Seven days after ligature placement, both groups were mated with normal male rats. The ligatures remained throughout pregnancy until weaning, after which the male offspring were distributed into groups: CN-o, control rat offspring; and PD-o, periodontal disease rat offspring. The body weight from 0 to 75days of age was measured. At 75days, the glycemia, insulinemia, TNF-α levels, Akt serine phosphorylation, and GLUT4 content in the GSM were measured in the offspring.
The PD-o group showed a low birth weight (LBW), unchanged glycemia, increased insulinemia, insulin resistance, increased TNF-α levels, decreased Akt serine phosphorylation status, and reduced GLUT4 content in the plasma membrane and translocation index after insulin stimulation.
Maternal periodontal disease causes LBW, insulin resistance, and alterations in the final stage of insulin signaling in the GSM of adult offspring.
胎儿编程假说表明，宫内刺激可诱导后代代谢变化，增加成年后患疾病的风险。牙周疾病可能会提高血清细胞因子水平。诸如肿瘤坏死因子-α（TNF-α）等细胞因子与葡萄糖转运蛋白4（GLUT4）表达降低、蛋白激酶B（Akt）磷酸化减少以及胰岛素抵抗有关。本研究旨在评估牙周疾病大鼠后代的腓肠肌骨骼肌（GSM）中GLUT4含量、Akt丝氨酸磷酸化状态、血糖、胰岛素水平及体重变化。
将雌性Wistar大鼠分为对照组（CN）和实验性牙周疾病组（PD），在其下颌第一磨牙周围放置结扎线。放置结扎线7天后，两组均与正常雄性大鼠交配。结扎线在整个孕期直至断奶时一直保留，之后雄性后代被分为几组：CN-o，对照大鼠后代；PD-o，牙周疾病大鼠后代。测量0至75日龄的体重。在75日龄时，测量后代的血糖、胰岛素水平、TNF-α水平、Akt丝氨酸磷酸化、GSM中的GLUT4含量。
PD-o组出生体重低（LBW），血糖无变化，胰岛素水平升高，存在胰岛素抵抗，TNF-α水平升高，Akt丝氨酸磷酸化状态降低，胰岛素刺激后质膜中GLUT4含量及转位指数降低。
母体牙周疾病会导致成年后代出生体重低、胰岛素抵抗以及腓肠肌骨骼肌胰岛素信号传导终末阶段的改变。
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