We next hypothesized that the administration of a full-length recombinant REG3A protein (rcREG3A, ALF5755) would improve metabolic homeostasis and insulin resistance and tested that hypothesis first in the ob/ob mice, a congenital leptin-deficient model of severe obesity, hyperinsulinemia and insulin resistance. Here, REG3A is linked to obesity due to melanocortin 4 receptor deficiency.