Adaptación metabólica y estructural de los tejidos mitóticos y postmitóticos a condiciones de restricción calórica en el ratón. Efecto del tipo de grasa en la dieta

• Autores: Husam Al Shaikh S. Khraiwesh
• Directores de la Tesis: José Manuel Villalba Montoro (dir. tes.)
• Lectura: En la Universidad de Córdoba (ESP) ( España ) en 2016
• Idioma: español
• Tribunal Calificador de la Tesis: José Peña Amaro (presid.), Francisco Javier Alcain Tejada (secret.), Fabien Pierrel (voc.)
• Materias:
  • Ciencias médicas
    • Ciencias clínicas
• Enlaces
  • Tesis en acceso abierto en: Helvia
• Resumen

  • In this work it is analyzed the effect of aging and its possible prevention by calorie restriction (CR) in liver and skeletal muscle from mice. These organs were selected as models of mitotic and post-mitotic tissues, respectively. Furthermore, the effect of dietary fat under CR was also investigated. For this purpose, animals submitted to CR were separated into three CR groups with soybean oil (high in ω−6 polyunsaturated fatty acids), fish oil (with a high content of polyunsaturated ω-3 fatty acids) and lard (rich in saturated and monounsaturated fatty acids). Soybean oil was the fat source in control ad libitum fed animals. After 6 and 18 months of CR, animals were killed and different morphological and functional parameters of both organs were studied. In liver, our results show that CR induced changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. Also, mean number of mitochondrial cristae and lengths were significantly higher in all CR groups compared with controls. CR had no remarkable effects on the expression levels of fission (Fis1 and Drp1) and fusion (Mfn1, Mfn2 and OPA1) protein markers after 18 months of CR. However, considerable differences in many of these parameters were found when comparing the CR groups. On the other hand, aging, CR and fat source are all factors that may influence apoptotic signaling in liver. For this reason the combined effect of these factors on a number of apoptosis regulators and effectors were studied as well. An age-linked increase in the mitochondrial apoptotic pathway was detected with CR, including a decrease in Bcl-2/Bax ratio, an enhanced release of cytochrome c to the cytosol and higher caspase-9 activity. Apoptotic index (DNA fragmentation) and mean nuclear area were increased in aged animals with the exception of calorie-restricted mice fed a lard-based fat source. In skeletal muscle, 6 and 18 months of CR partially prevented the decreased size of red and white fibers observed in aged control mice. At the ultrastructural level, mean area of myofibrils and planimetric parameters of subsarcolemmal and intermyofibrilar mitochondria also changed during aging and in the different groups of CR and similar results were obtained when the expression levels of protein related to mitochondrial fission, fusion and function (Sirt3 and VDAC) were analyzed...