Molina-Aguilar Christian, Guerrero-Carrillo María de Jesús, Espinosa-Aguirre Jesús Javier, Olguin-Reyes Sitlali, Castro-Belio Thania, Vázquez-Martínez Olivia, Rivera-Zavala Julieta Berenice, Díaz-Muñoz Mauricio
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México.
Faculta de Ciencias Naturales, Universidad Autónoma de Querétaro, Querétaro, México.
Carcinogenesis. 2017 Aug 1;38(8):847-858. doi: 10.1093/carcin/bgx052.
Hepatocellular cancer is the most common type of primary liver cancer. Cirrhosis is the main risk factor that generates this malady. It has been proven that caloric restriction protocols and restricted feeding schedules are protective in experimental carcinogenic models. We tested the influence of a time-caloric restriction protocol (2 h of food access during the daytime for 18 weeks) in an experimental model of cirrhosis-hepatocarcinoma produced by weekly administration of diethylnitrosamine. Our results indicate that time-caloric restriction reduced hepatomegaly and prevented the increase in blood leukocytes promoted by diethylnitrosamine. Strikingly, time-caloric restriction preserved functional and histological characteristics of the liver in fibrotic areas compared to the cirrhotic areas of the Ad Libitum-fed group. Tumoural masses in the restricted group were well differentiated; consider a neoplastic or early stage of HCC. However, time-caloric restriction enhanced collagen deposits. With regard to the cancerous process, food restriction prevented systemic inflammation and an increase in carcinoembryonic antigen, and it favoured the occurrence of diffuse multinodular tumours. Histologically, it prevented hepatocyte inflammation response, the regenerative process, and neoplastic transformation. Time-caloric restriction stimulated circadian synchronization in fibrotic and cancerous liver sections, and it increased BMAL1 clock protein levels. We conclude that time-caloric restriction prevents fibrosis from progressing into cirrhosis, thus avoiding chronic inflammation and regenerative processes. It also prevents, probably through circadian entrainment and caloric restriction, the neoplastic transformation of tumoural lesions induced by diethylnitrosamine.
肝细胞癌是原发性肝癌最常见的类型。肝硬化是引发这种疾病的主要危险因素。业已证明，热量限制方案和限时进食时间表在实验性致癌模型中具有保护作用。我们在通过每周给予二乙基亚硝胺构建的肝硬化 - 肝癌实验模型中，测试了限时热量限制方案（白天18周内有2小时进食时间）的影响。我们的结果表明，限时热量限制减少了肝肿大，并阻止了二乙基亚硝胺所促进的血液白细胞增加。令人惊讶的是，与自由进食组的肝硬化区域相比，限时热量限制保留了纤维化区域肝脏的功能和组织学特征。限制组的肿瘤块分化良好；考虑为肿瘤性或肝癌早期阶段。然而，限时热量限制增强了胶原沉积。关于癌变过程，食物限制可防止全身炎症和癌胚抗原增加，并有利于弥漫性多结节肿瘤的发生。从组织学上看，它可防止肝细胞炎症反应、再生过程和肿瘤转化。限时热量限制刺激了纤维化和癌性肝组织切片中的昼夜节律同步，并增加了BMAL1时钟蛋白水平。我们得出结论，限时热量限制可防止纤维化进展为肝硬化，从而避免慢性炎症和再生过程。它还可能通过昼夜节律调整和热量限制，防止二乙基亚硝胺诱导的肿瘤病变发生肿瘤转化。
