Expresión de caveolinas en músculo esquelético y adipocitos de tejido adiposo blanco de ratas alimentadas con una dieta hipercalórica rica en grasa. Relación con la señalización insulínica

Resumen

A great number of genes have been related to obesity and insulin resistance, such as the caveolin family which is formed by 3 different genes coding respectively for caveolin 1, 2 and 3 (Cav-1, Cav-2 and Cav-3). Cav-1 and Cav-2 are co-expressed in many well differentiated cell types, such as endothelial or alveolar cells, and especially in adipocytes, whereas Cav-3 expression is restricted exclusively to skeletal and cardiac muscle tissue. The aim of this project has been to study how a high-fat cafeteria diet influences the expression and activation of the three caveolins and the possible effect of these variations in the insulin signalling cascade. The study was carried out in skeletal muscle, and adipocytes isolated from retroperitoneal and subcutaneous white adipose tissue, since in all these tissues there is a high level of caveolin expression. Rats fed on a cafeteria diet constitute an obesity model with similarities to common human obesity, since it is also based on excessive energy consumption. Results obtained in skeletal muscle show a three phase response to cafeteria diet. An initial and fast response that could act as a defence mechanism against the overload of nutrients, in which the expression and activity of the insulin pathway, as well as that of the caveolins, are increased. This is followed by a delayed response (after 35 days of diet), characterized by the establishment of an insulin resistant metabolism, accompanied with a decrease of both, insulin pathway and Cav-1 activity. Finally after 72 days of diet a chronic phase is set up, in which insulin resistance is firmly settled, and the insulin pathway as well as caveolins are clearly inactive. Data obtained for adipocytes isolated from retroperitoneal and subcutaneous adipose tissue indicate two time-dependent responses to the cafeteria diet that influence insulin signalling and caveolins expression and activation. An early high fat diet resistance response which involves retroperitoneal adipocytes, and a late adaptive response affecting mainly to subcutaneous adipocytes. Finally differences between fasted and non fasted animals are more evident in those fed with a control diet than in those fed with the high-fat diet, whose metabolism is altered after 72 days. These differences concern insulin receptor and Cav-1 activation as well as GLUT-4 expression indicating that food intake may change these parameters.