neuropeptide-y and Protein-Energy-Malnutrition

To assess whether endocrine dysfunction may cause derangement in energy homeostasis in patients undergoing hemodialysis (HD), we profiled hormones, during a 3-day period, from the adipose tissue and the gut and the nervous system around the circadian clock in 10 otherwise healthy HD patients and 8 normal controls. The protocol included a 40-h fast. We also measured energy-protein intake and output and assessed appetite and body composition. We found many hormonal abnormalities in HD patients: 1) leptin levels were elevated, due, in part, to increased production, and nocturnal surge in response to daytime feeding, exaggerated. 2) Peptide YY (PYY), an anorexigenic gut hormone, was markedly elevated and displayed an augmented response to feeding. 3) Acylated ghrelin, an orexigenic gut hormone, was lower and did not exhibit the premeal spike as observed in the controls. 4) neuropeptide Y (NPY), a potent orexigenic peptide, was markedly elevated and did not display any circadian variation. 5) Norepinephrine, marginally elevated, did not exhibit the normal nocturnal dip. By contrast, α-melanocyte-stimulating hormone and glucagon-like peptide-1 were not different between the two groups. Despite these hormonal abnormalities, HD patients maintained a good appetite and had normal body lean and fat mass, and there was no evidence of increased energy expenditure or protein catabolism. We explain the hormonal abnormalities as well as the absence of anorexia on suppression of parasympathetic activity (vagus nerve dysfunction), a phenomenon well documented in dialysis patients. Unexpectedly, we noted that the combination of high leptin, PYY, and NPY with suppressed ghrelin may increase arterial blood pressure, impair vasodilatation, and induce cardiac hypertrophy, and thus could predispose to adverse cardiovascular events that are the major causes of morbidity and mortality in the HD population. This is the first report attempting to link hormonal abnormalities associated with energy homeostasis to adverse cardiovascular outcome in the HD patients.

Topics: Adult; Anorexia; Appetite; Body Composition; Cardiovascular Diseases; Circadian Rhythm; Endocrine System Diseases; Energy Metabolism; Fasting; Female; Ghrelin; Homeostasis; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Peptide YY; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency; Risk Factors

Effects of infusions of neuropeptide Y (NPY) into 3rd ventricle of growing sheep fed on diets containing restricted (R) or elevated (E) levels of protein on the immunoreactive (ir) somatostatin neurones, ir somatotrophs, growth hormone (GH) concentration in the blood plasma were studied. The long-term restriction of protein in the diet elicited: enhancing irSS content in periventricular perikarya; diminishing irSS stores in the median eminence and elevating the number ir somatotrophs and content of irGH. NPY infusions enhanced the content of irSS in perikarya in sheep fed on E diet and diminished the number of ir somatotrophs and content of irGH of sheep fed on R diet. The R diet as well as NPY infusions caused an increase in GH mean concentrations in the blood plasma. Obtained results suggest that stimulatory effect of restricted feeding and/or NPY action on GH secretion can be due to attenuated SS output. Since dietary restrictions and exogenous NPY have similar influence on the activation of GH secretion, we suggest that NPY could be a neuromodulatory link between nutritional cues and somatotropic axis in sheep.

Topics: Animals; Body Weight; Diet, Protein-Restricted; Dietary Proteins; Female; Growth Hormone; Hypothalamo-Hypophyseal System; Injections, Intraventricular; Insulin-Like Growth Factor I; Median Eminence; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Anterior; Protein-Energy Malnutrition; Sheep; Somatostatin

Maternal low-protein malnutrition during gestation and lactation (LP) is an animal model frequently used for the investigation of long-term deleterious consequences of perinatal growth retardation. Hypothalamic neuropeptides are decisively involved in the central nervous regulation of body weight and metabolism. We investigated neuropeptide Y (NPY) in distinct hypothalamic nuclei in the offspring of LP mother rats at the end of the critical hypothalamic differentiation period (20th day of life). Weanling LP offspring were underweight (P< 0.001) and hypoinsulinaemic (P< 0.05), while leptin levels were unchanged. NPY was significantly increased in the paraventricular hypothalamic nucleus (PVN) (P< 0.01) and lateral hypothalamic area (P< 0.05) in LP offspring. In contrast, NPY was unchanged in the ventromedial hypothalamic nucleus (VMN). These observations indicate a leptin-independent stimulation of the orexigenic ARC-PVN axis in undernourished LP rats at weaning. Furthermore a disturbed NPYergic regulation of the VMN is suggested, possibly contributing to alterations of the hypothalamic regulation of body weight and metabolism in LP offspring during life.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Body Weight; Female; Hypothalamic Area, Lateral; Hypothalamus; Insulin; Leptin; Male; Median Eminence; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Protein-Energy Malnutrition; Rats; Rats, Wistar; Ventromedial Hypothalamic Nucleus; Weaning

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