leptin and xenin-25

Recent studies have shown that xenin can act in the hypothalamus, reducing food intake through a leptin- and melanocortin system-independent mechanism.. To evaluate the impact of body mass reduction on the blood and cerebrospinal fluid (CSF) levels of xenin.. Thirteen obese patients (11 women) selected for roux-in-Y gastric bypass surgery were evaluated before and approximately 8 months after surgery. Xenin was determined in serum and CSF by radioimmunoassay.. As compared with lean subjects, obese patients have increased blood levels of xenin, which reduce after surgery. There are significant correlations between blood xenin and blood leptin and insulin levels. CSF concentration of xenin is ∼10-fold lower than blood levels, and is significantly higher in obese subjects as compared with lean ones, returning to normal levels after body mass reduction. There is a significant linear correlation between CSF and blood levels of xenin.. Xenin is present in the human CSF in a concentration ∼10-fold lower than the blood. Both blood and CSF xenin are correlated with blood levels of important markers of adiposity, leptin and insulin. The levels of CSF xenin are linearly correlated with blood xenin, independently of patient body mass, suggesting that either its transport across the blood-brain barrier is not saturated in the concentration range detected in this study or that there is a coordinated release of xenin from the periphery and the CNS.

Topics: Adolescent; Adult; Biological Transport; Biomarkers; Blood-Brain Barrier; Body Mass Index; Fasting; Female; Gastric Bypass; Humans; Leptin; Male; Middle Aged; Neurotensin; Obesity, Morbid; Radioimmunoassay; Weight Loss

Xenin, a 25-amino acid peptide, was initially isolated from human gastric mucosa. Plasma levels of xenin rise after a meal in humans, and administration of xenin inhibits feeding in rats and chicks. However, little is known about the mechanism by which xenin regulates food intake. Signaling pathways including leptin and melanocortins play a pivotal role in the regulation of energy balance. Therefore, we addressed the hypothesis that xenin functions as a satiety factor by acting through the melanocortin system or by interacting with leptin.. The effect of intracerebroventricular and intraperitoneal administration of xenin on food intake was examined in wild-type, agouti, and ob/ob mice. The effect of intracerebroventricular injection of SHU9119, a melanocortin receptor antagonist, on xenin-induced anorexia was also examined in wild-type mice. To determine whether the hypothalamus mediates the anorectic effect of xenin, we examined the effect of intraperitoneal xenin on hypothalamic Fos expression.. Both intracerebroventricular and intraperitoneal administration of xenin inhibited fasting-induced hyperphagia in wild-type mice in a dose-dependent manner. The intraperitoneal injection of xenin also reduced nocturnal intake in ad libitum-fed wild-type mice. The intraperitoneal injection of xenin increased Fos immunoreactivity in hypothalamic nuclei, including the paraventricular nucleus and the arcuate nucleus. Xenin reduced food intake in agouti and ob/ob mice. SHU9119 did not block xenin-induced anorexia.. Our data suggest that xenin reduces food intake partly by acting through the hypothalamus but via signaling pathways that are independent of those used by leptin or melanocortins.

Topics: Animals; Eating; Fasting; Hypothalamus; Immunohistochemistry; Leptin; Male; Melanocortins; Melanocyte-Stimulating Hormones; Mice; Mice, Inbred C57BL; Mice, Obese; Neurotensin; Oncogene Proteins v-fos; Peptides; Receptors, Melanocortin; Signal Transduction