OBJECTIVE: Leptin, neuropeptide-Y (NPY) and orexin are peptides regulating energy metabolism and appetite control. NPY and orexin are mainly found in the central nervous system and they have also recently been found in the peripheral nervous system. We investigated how fasting affects changes in circulating concentrations of these peptides and their association with nutritional and metabolic parameters in humans. DESIGN AND METHODS: Ten non-obese female patients with psychosomatic disorders fasted for 7 or 10 days. Blood samples were collected at 0800 h before fasting, on the 3rd and 7th days during the fast (with an additional sample taken on the 10th day when the fasting continued for 10 days) and on the 3rd and 7th days of refeeding. We measured blood concentrations of orexin-A, NPY, leptin, adrenocorticotropin, cortisol, insulin, C-peptide, glucose, and beta-hydroxybutyrate. RESULTS: Body mass index and plasma leptin concentrations concomitantly and significantly decreased during fasting, whereas serum orexin-A concentrations significantly increased and were negatively correlated with plasma leptin concentrations. Plasma NPY concentrations decreased slightly but were not significantly different from the prefasting values, and no significant relationship with leptin or orexin-A was found. Orexin-A and leptin concentrations showed a significant inverse correlation with serum glucose, insulin, C-peptide, and beta-hydroxybutyrate concentrations. Only changes in plasma leptin concentrations showed a significant negative correlation with serum cortisol concentrations. All the measured indices which changed during fasting returned to the prefasting concentrations by the 7th day of refeeding. CONCLUSION: Peripheral orexin-A and leptin concentrations inversely change during fasting, which is significantly correlated with energy metabolism in humans.
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