neuropeptide-y and Nutrition-Disorders

A reduction in the availability of oxygen and nutrients across the placenta in the last trimester of pregnancy may lead to intrauterine growth retardation (IUGR) which, in turn, may cause a persistent postnatal growth failure. However, it is unknown whether this persistent growth retardation is centrally mediated through alterations in the components of the growth hormone (GH)-axis. We tested the hypothesis that alterations in the development of the central components of the GH-axis contribute to the persistent growth failure observed after experimentally induced IUGR or early postnatal food restriction (FR) in the rat. Using semi-quantitative in situ hybridization, we compared somatostatin (SS), GH-releasing hormone (GHRH) and neuropeptide Y (NPY) mRNA levels in adult rats experimentally subjected to IUGR or FR. We report that IUGR increased the expression of SS mRNA in the periventricular nucleus (PeN) of adult male and female rats by 128% and 153% respectively, did not alter the expression of GHRH mRNA in the arcuate nucleus (ARC) and decreased the NPY mRNA expression in the ARC by 73% in males and 61% in females, whereas in the FR group no changes in the expression of these mRNAs were observed. These data show that the timing of malnutrition or the presence of the placenta is important for the long-term alterations since the effects only occurred in the prenatally induced growth retardation and not in the early postnatally induced growth retardation group.

Topics: Animals; Female; Fetal Growth Retardation; Food Deprivation; Gene Expression Regulation; Growth Hormone-Releasing Hormone; In Situ Hybridization; Male; Neurons; Neuropeptide Y; Neuropeptides; Nutrition Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; RNA, Messenger; Somatostatin

We have characterized the localization and the ontogenetic changes in Neuropeptide tyrosine (NPY) before birth and investigated the regulation of NPY expression by cortisol and undernutrition in the fetal sheep hypothalamus during late gestation. Using immunohistochemistry, we have identified NPY-containing neurons in the infundibular nucleus and the internal layer of the median eminence in fetal hypothalami collected between 110 and 147 days gestation. NPY projections were also present in the paraventricular nucleus (PVN) of fetal hypothalami at all ages between 110 days gestation and term. There was a significant increase in the amount of immunoreactive NPY/g hypothalamus between 87 and 113 days and 131-140 days gestation and a further significant increase after 141 days gestation. The total hypothalamic content of immunoreactive NPY increased significantly between 87 and 113 days and 141-145 days gestation. The levels of NPY mRNA: 18S rRNA in the mediobasal region of the fetal hypothalamus were significantly higher at 145-146 days gestation than at any earlier gestational age between 116 and 141 days gestation. Cortisol (2.5-3.0 mg/24 h) was infused intrafetally between 109 and 116 days gestation. The ratio of NPY mRNA: 18s rRNA in the mediobasal region of the fetal hypothalamus was significantly higher in the cortisol-infused group when compared with the saline-infused control group at 116 days gestation. Maternal, and hence fetal undernutrition, was induced between 110 and 146 days gestation. At 145-146 days gestation the ratio of NPY mRNA: 18S rRNA in the mediobasal region of the fetal hypothalamus was significantly higher in the undernutrition group when compared with control animals. We have therefore demonstrated that NPY is present in the hypothalamus of the sheep fetus before birth and that hypothalamic NPY content and NPY mRNA increase before delivery. We have also found that glucocorticoids and undernutrition stimulate increases in NPY mRNA levels in the hypothalamus before birth.

Topics: Animals; Blood Glucose; Blotting, Northern; Female; Fetus; Gestational Age; Hydrocortisone; Hydrogen-Ion Concentration; Hypothalamus; Immunohistochemistry; Neuropeptide Y; Nutrition Disorders; Pregnancy; Pregnancy, Animal; Sheep

Malnutrition has definitely been related to mortality among dialysis patients. Persistent loss of appetite is one of the major symptoms found in these patients. It is also well recognized that several substances produce anorexia or disorders of the hunger-satiety cycle in several diseases. The aim of this study was to identify the role of anorexigen substances (TNF-alpha and cholecystokinin or CCK) and an orexigen substance (neuropeptide Y or NPY) in anorexia and malnutrition among 55 clinically stable peritoneal dialysis (PD) patients.. High TNF-alpha plasma levels were found in 41 of 42 patients (97.6%) with a mean of 70.5+/-32.3 pg/ml. Patients with anorexia (n=11) or anorexia with nausea or vomiting (n=5) had higher TNF-alpha values than patients without these symptoms (75.9+/-34 vs 52.1 +/-24.5 pg/ml, P<0.05). Eight patients with a prior diagnosis of acid pylori disease showed higher TNF-alpha values (87.2+/-24.3) than 30 unaffected patients (63.6+/-30.5, P<0.05). TNF-alpha showed a significant negative linear correlation with retinol binding protein (RBP) (r=-0.37, n=34, P<0.05), and venous pH (r=-0.4, n=42, P<0.01); also, TNF-alpha values higher than 65 pg/ml were inversely associated with transferrin, cholesterol, blood urea nitrogen (BUN) and CCK. Patients with prealbumin levels lower than 30 mg/dl, a BMI lower than 30 kg/m2, nPCR lower than 1.1 g/kg/day and urea KT/V lower than 2.2 showed higher serum TNF-alpha levels. Patients who had been on CAPD treatment for longer periods showed higher TNF-alpha values. High plasma CCK levels were found in 38 of 45 patients (84%), mean 45.9+/-32.3 pg/ml. Patients with anorexia had no difference in CCK values compared with those without. A direct association was found between CCK levels and some nutritional markers (albumin, fibronectin, triglycerides, folic acid and nPCR in non diabetic patients). Although CCK has a recognized anorectic effect, this direct association might be because of an abnormal stimulation of CCK glucose feedback (trypsin) due to continuous peritoneal glucose absorption. This suggests that CCK could be an immediate food intake marker in PD patients. The NPY plasma levels were normal in 33 patients, high in 6 and low in 11. Patients with anorexia showed lower NPY levels than those without. NPY values greater than 50 pg/ml were directly associated with higher transferrin, prealbumin, RBP, nPCR and urea KT/V values. Importantly, a negative linear correlation between NPY and TNF-alpha was found (r=-0.42, n= 41, P<0.01). There was no significant relationship between residual renal clearance and the serum levels of the three peptides.. In conclusion, our data suggest that high TNF-alpha and low NPY serum levels are associated with anorexia. High TNF-alpha, low CCK and low NPY serum levels are also related to a poor nutritional status. Further research on these circulating substances is required.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Biomarkers; Cholecystokinin; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Neuropeptide Y; Nutrition Disorders; Nutritional Status; Peritoneal Dialysis; Protein-Energy Malnutrition; Tumor Necrosis Factor-alpha

Down-regulation of thyroid activity during underfeeding or diabetes - and upregulation during overfeeding - have not been adequately explained. Experimental findings suggest that hypothalamic secretion of thyrotropin releasing hormone (TRH) is modulated by feeding status; neuropeptide Y may be a key mediator of this modulation. I propose that insulin, acting centrally as a signal of carbohydrate availability, promotes TRH secretion by inhibiting release of neuropeptide Y in the paraventricular nucleus. This mechanism may contribute to the weight loss reported during administration of certain insulin-sensitizing agents, and observed during low-fat diets.

Topics: Animals; Diabetes Mellitus; Homeostasis; Humans; Insulin; Models, Biological; Neuropeptide Y; Nutrition Disorders; Paraventricular Hypothalamic Nucleus; Thyroid Gland; Thyrotropin-Releasing Hormone