Effect of nutrition on plasma C-type natriuretic peptide forms in adult sheep: evidence for enhanced C-type natriuretic peptide degradation during caloric restriction

Abstract

Previous studies in lambs and children show that the plasma concentration of amino terminal pro–C-type natriuretic peptide (NTproCNP), a stable product of proCNP, is strongly correlated with skeletal growth and markers of bone formation. Consistent with these findings, CNP expression is sensitive to nutritional status and is reduced by caloric restriction (CR) in both the fetus and the postnatal lamb. However, the effect of nutritional status on CNP in the adult, once linear growth is complete, is unknown. Hypothesizing that reduced CNP synthesis during CR is contingent on the presence of active growth plates, we studied the effect of CR ( 25% of maintenance) or loading (CL, 200% of maintenance) on CNP forms and alkaline phosphatase (ALP) in adult ewes and compared the findings to responses in a control group (C) fed a maintenance diet of 10.6 MJ of metabolizable energy. Live body weight was reduced (17%) in the CR group and increased (10%) in the CL group after 16 days of intervention. Plasma CNP concentration and ALP both fell in CR sheep and were significantly lower than C ( P < .05 for both), returning toward basal levels 1 week after refeeding. In contrast, plasma NTproCNP did not differ (CR vs C). There were no significant changes in CNP forms and ALP in CL sheep compared with C. Fall in plasma CNP but not in NTproCNP in CR adult sheep suggests that CNP degradation (not synthesis) is altered, and contrasts with previous findings in growing lambs where CR reduces both CNP forms.