This family includes calcitonin (CT), its precursor procalcitonin (PCT), and alpha calcitonin-gene related peptide (αCGRP), which are all encoded by the gene Calca. Here, we studied the role of Calca-derived peptides in diet-induced obesity (DIO) by challenging Calcr−/− (encoding the calcitonin receptor, CTR), Calca−/−, and αCGRP−/− mice and their respective littermates with high-fat diet (HFD) feeding for 16 weeks. The gene discussed is CALCR; the disease is obesity due to melanocortin 4 receptor deficiency.