Thus, the present study was done to elucidate the role of DEP-1 in insulin signaling, including its potential binding to the tyrosine phosphorylated insulin receptor, and to investigate the effects of ASOs targeting DEP-1 (ISIS 285564) in a metabolic high-fat diet-induced obesity model characterized by reduced insulin sensitivity. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.