| abstract |
Autophagy is typically activated by starvation, allowing cells and organisms to mobilize their energy reserves. It is known that the pharmacological modulation of autophagy represents a therapeutic potential. The inventors have demonstrated here that a protein that is released from cells in an unconventional, autophagy-dependent manner, namely, a diazepam binding inhibitor (DBI), regulates autophagy. In particular, the inventors demonstrate that DBI inhibits autophagy and that the recombinant DBI supply to mice improves glycolysis, improves lipogenesis and inhibits fatty acid oxidation. The inventors have shown that the neutralization of DBI by a monoclonal antibody and an active immunization by means of an immunogenic derivative of DBI causing autoantibodies induce autophagy and lead to metabolic changes which increase the weight loss induced by the starvation, reduce food intake during re-feeding, and reduce weight gain in response to high calorie diets. Accordingly, the present invention relates to methods and pharmaceutical compositions for modulating autophagy based on modulating DBI activity or expression. |