Metabolic response in blood and cerebrospinal fluid during feed restriction: Identification of potential metabolic signals associated with individual feed intake rebound

The aim of this study was to evaluate the effects of feed restriction and refeeding on metabolic and AA profiles in blood serum, and on cerebrospinal fluid (CSF) profiles during the feed restriction period, using a controlled feeding model. Additionally, the study aims to identify metabolic signals generated during feed restriction that may help explain individual variability in the feed intake recovery. Following 2 wk of adaptation, 8 primiparous Holstein cows housed in individual stalls with free access to water were fed ad libitum for 5 d (basal period), followed by 50% feed restriction for 5 d, and then returned to ad libitum feeding for 5 d (refeeding period). Dry matter intake and milk yield were determined daily. On d 4, 9, and 14 before morning feeding, blood serum samples were collected by puncture of the coccygeal vessels, whereas CSF samples were obtained from the cisterna magna on d 4 and 9. A targeted analysis of AA was performed using GC time-of-flight MS method in both fluids. The blood serum metabolite and hormone concentrations were affected by the period. In general, more significant increases in AA concentrations were observed in the CSF during feed restriction compared with blood serum, particularly for EAA and branched-chain AA. In blood serum, only a few AA showed significant changes during the refeeding period, whereas in CSF several AA, including Val, Glu, and Lys, increased during feed restriction. A partial least squares regression model using CSF data successfully predicted feed intake rebound measured as the change in the DMI (ΔDMI) during the refeeding relative to feed restriction. This model included 12 predictors; among them, Cys showed a positive association with the ΔDMI, whereas the other AA and glucose exhibited a negative association. In contrast, no valid model was obtained when using serum AA concentrations as predictors. Short-term feed restriction induced metabolic, hormonal, and AA changes in both serum and CSF. Variability in refeeding response was linked to CSF glucose and AA concentrations during restriction, suggesting that altered blood-brain barrier selectivity or central AA production may be associated with feed intake regulation.