Methods and compositions are provided for modulating fat storage of animals by targeting the gene and gene products of cathepsins, particularly cathepsins L, K, and S. The method comprises: administering to the animal an agent that reduces an in vivo level of cathepsin L activity such that fat storage by the animal is reduced. The methods of the present invention can be used to diagnose obesity, diabetes and related diseases such as hyperinsulinmia, hyperglycermia, hypertension, cardiovascular diseases, muscular dystrophy and infertility, as well as screen for agents that can be used threapeutics for these diseases.