‘MitoCholERaxis’: new tools against obesity-related diseases

Gemma Fabriàs Domingo, Mª del Carmen García Ruiz, Josefina Casas Brugulat and Nuria Bielsa Viladarga,  Consejo Superior de Investigaciones Científicas (CSIC).

The ultimate aim is to help identify new treatments for obesity-related diseases. Fatty liver is characterized by the accumulation of cholesterol in the liver cells or hepatocytes. The cholesterol molecules build up in the mitochondria, the cell components that supply the cell with energy and therefore play a key role in metabolism.

And it is obesity that triggers this whole process. Obesity, we now know, disrupts the functioning of the endoplasmic reticulum, the cell organelle that assures the quality of proteins. This project pursues a deeper understanding of the linkage between endoplasmic reticulum impairment and StARD1-mediated mitochondrial cholesterol accumulation. The working hypothesis is that endoplasmic reticulum malfunction due to the onset of obesity causes increased expression of the StARD1 protein, responsible precisely for carrying cholesterol to the mitochondria.

The team will use an obesogenic diet to induce obesity in mice that have been genetically modified to turn off hepatocyte production of StARD1, in the belief that demonstrating this protein’s vital implication in fatty liver disease may open up significant avenues for its future treatment.