Natriuretic Peptide Family Protein (NPFP) has been identified as a secretory peptide produced by muscle and functions in regulating cellular metabolism. In a microarray analysis with muscle from muscle-specific CR6 interacting factor 1 (Crif1) deletion mouse which showed severe loss of body weight, NPFP level was dramatically increased but the function of NPFP in regulating appetite in hypothalamus was not known. Firstly, we tried to perform intracerebroventricular injection of NPFP recombinant peptide to the B6 mice and it showed 20 percent reduction of food intake. Furthermore, NPFP mRNA expression was tightly regulated by nutritional status as shown in mouse muscle which was downregulated under starvation condition and increased by refeeding. Also, in ob/ob mouse, mRNA expression in muscle and plasma level of NPFP was significantly induced. Underlying mechanism that food intake reduction by NPFP is partly via increase of cGMP level. Recombinant NPFP treatment enhanced cGMP production by C type natriuretic peptide in N1 hypothalamic cells which expresses both NPFP receptor and CNP receptor. Taken together, NPFP has a function in central regulation of appetite by modulating cGMP level in hypothalamic neuron.