BACKGROUND

<em>Nesfatin</em>-<em>1</em>, a recently discovered anorexigenic peptide, is expressed in several tissues, including pancreatic islet cells and central nervous system. However, its pathophysiological role in the development of obesity and insulin resistance remains unknown.

OBJECTIVE

To investigate the possible involvement of nesfatin-<em>1</em> in the pathogenesis of childhood obesity, we examined the relationship between fasting and postprandial nesfatin-<em>1</em> concentrations and metabolic/antropometric parameters in obese children.

METHODS

The study included obese children with a body mass index >95th percentile. Fasting serum glucose, insulin, lipid profile, fasting and postprandial (<em>1</em>20th min) nesfatin-<em>1</em> levels were measured to evaluate the metabolic parameters. Different cutoff values for prepubertal and pubertal stages were used to determine the status of insulin resistance (HOMA-IR) (prepubertal >2.5, pubertal >4). The percentage of body fat was measured using bioelectric impedance analysis.

RESULTS

Seventy-one obese children were included in this study. There was no statistically significant difference between fasting and postprandial nesfatin-<em>1</em> levels in obese subjects (0.70 ± 0.<em>1</em>5 and 0.69 ± 0.<em>1</em>4 ng/mL, p>0.05, respectively). Insulin resistance was observed in 58% (4<em>1</em>/7<em>1</em>) of the cases. There was no significant difference in either fasting or postprandial serum nesfatin-<em>1</em> levels between the insulin-resistant and non-resistant groups (p>0.05). There was no correlation between fasting and postprandial serum nesfatin-<em>1</em> levels and anthropometric and metabolic parameters in insulin-resistant and non-resistant groups.

CONCLUSIONS

In this study, there was no significant increase in the postprandial level of nesfatin-<em>1</em>. This observation suggested that oral glucose load in obese children may not be sufficient for nesfatin-<em>1</em> response and that nesfatin-<em>1</em> may not have an effect as a short-term regulator of food intake.

<em>Nesfatin</em>-<em>1</em> is a new energy-regulating peptide widely expressed at both central and peripheral tissues with pleiotropic effects. In the last years, the study of <em>nesfatin</em>-<em>1</em> actions and its possible implication in the development of different diseases has created a great interest among the scientific community. In this review, we will summarize <em>nesfatin</em>-<em>1</em> main functions, focusing on its cardiovascular implications.

The anorexigenic neuropeptide NEFA/nucleobindin 2 (NUCB2)/<em>nesfatin</em>-<em>1</em>-containing neurons are distributed in the brain regions involved in feeding regulation, including the hypothalamic paraventricular nucleus (PVN). Functionally, NUCB2/<em>nesfatin</em>-<em>1</em> neurons in the PVN regulate feeding through the hypothalamus and brain stem. However, the neural network of PVN NUCB2/<em>nesfatin</em>-<em>1</em> neurons has yet to be elucidated. Axon collateral branches allow individual neurons to target multiple neurons. In some cases, each target neuron can be located in different nuclei. Here we show that a single neuron in the PVN projects axonal collaterals to both the dorsal vagal complex (DVC) and the arcuate nucleus (ARC), which are important brain regions for feeding regulation. In this study, after injection of different retrograde tracers into the DVC and ARC, both tracer-labeled neurons were detected in the identical PVN neuron, indicating the axon collateral projections from the single PVN neuron to the DVC and ARC. Furthermore, immunohistochemical analysis revealed that approximately 50 % of the neurons with axon collateral projections from the PVN to the DVC and ARC were found to be NUCB2/<em>nesfatin</em>-<em>1</em> neurons. Our data suggest that a single NUCB2/<em>nesfatin</em>-<em>1</em> neuron in the PVN projects to both the ARC and the DVC with axon collateral projection. Although the physiological significance remains to be elucidated, our data offer new perspectives on NUCB2/<em>nesfatin</em>-<em>1</em> function at the neural network level and food intake regulation.

BACKGROUND

Elevated L-type Ca²⁺channel expression level increases Ca²⁺ influx. This can cause hypertrophy and pathological remodeling of the heart especially under stress conditions. <em>Nesfatin</em>-<em>1</em> can activate hypothalamic L, P and Q type Ca²⁺ channels and increase insulin secretion in pancreatic islet beta cells via activation of L-type Ca²⁺ channels. On the other hand, the effect of <em>nesfatin</em>-<em>1</em> on cardiac L-type Ca²⁺ channels has not been studied yet.

OBJECTIVE

We aimed to identify the effect of peripheral chronic <em>Nesfatin</em>-<em>1</em> application on cardiac L-type Ca²⁺ channel α<em>1</em>c subunit expression level in normal rats and those subjected to chronic restraint stress.

METHODS

Three-month aged Wistar albino rats were randomly divided into 4 groups (n = 7) as Control, Stress, Control+<em>Nesfatin</em>-<em>1</em>, and <em>Nesfatin</em>-<em>1</em>+Stress. Rats in groups subjected to restraint stress were placed in a specially built size-manipulable cabin for 2 h/day (between <em>1</em>0:00 and <em>1</em>2:00 a.m.) for <em>1</em>0 consecutive days without allowing water and food intake. <em>Nesfatin</em>-<em>1</em> segment (0.25 nmol/g bw intraperitoneally) was applied during the <em>1</em>0 consecutive days. Western blot analyses were performed to determine the expression level of L-type Ca²⁺ channel α<em>1</em>c subunit protein in rat cardiac extracts.

RESULTS

Cardiac L-type Ca²⁺ channel α<em>1</em>c subunit protein expression levels were increased significantly after chronic peripheral <em>Nesfatin</em>-<em>1</em> application in rats subjected to restraint stress (p = 0.032).

CONCLUSIONS

We can conclude that <em>Nesfatin</em>-<em>1</em> can cause cardiac failures during clinical treatments by elevating cardiac L-type Ca²⁺ channel α<em>1</em>c subunit protein expression level (Fig. 2, Ref. 26).

<em>Nesfatin</em>-<em>1</em> is a neuroendocrine peptide with potent anorexigenic activity in rodents. The potential role of <em>nesfatin</em>-<em>1</em> on the regulation of energy balance, metabolic functions and inflammation is currently debated in obese humans. In the present study, <em>nesfatin</em>-<em>1</em> fluctuations and their associations with metabolic factors were investigated in severely obese patients who underwent biliopancreatic diversion with duodenal switch (BPD/DS) and severely obese controls (SOC).

Sixty severely obese patients who underwent BPD/DS and <em>1</em>5 SOC (matched for BMI and age) were included in the study. Associations between <em>nesfatin</em>-<em>1</em> levels and body composition, glucose metabolism, lipid profile as well as inflammatory markers were evaluated at baseline and over a post-surgery<em>1</em>2-month (<em>1</em>2M) period.

Body weight was reduced at 6M and at <em>1</em>2M in BPD/DS patients (P<0.00<em>1</em>). <em>Nesfatin</em>-<em>1</em> levels were reduced at 6M (women: P<0.05) and at <em>1</em>2M (men and women; P<0.00<em>1</em>) in BPD/DS patients. At baseline, <em>nesfatin</em>-<em>1</em> levels negatively correlated with weight, fat (FM) and fat-free mass (FFM) in the whole population (combined BPD/DS and SOC patients). At <em>1</em>2M, <em>nesfatin</em>-<em>1</em> concentrations positively correlated with weight, FM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, triglyceride and apoB values. At <em>1</em>2M, % changes in <em>nesfatin</em>-<em>1</em> were positively associated with% changes in weight, FM, FFM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, apoB and C-reactive protein.

<em>Nesfatin</em>-<em>1</em> levels decrease following BPD/DS-induced weight loss and are significantly associated with parameters of metabolic health.

Ghrelin and <em>nesfatin</em>-<em>1</em> are two peptidyl hormones primarily involved in food intake regulation. We previously reported that the amount of dietary carbohydrates, protein and lipids modulates the expression of these peptides in goldfish in vivo. In the present work, we aimed to characterize the effects of single nutrients on ghrelin and <em>nesfatin</em>-<em>1</em> in the intestine and hepatopancreas. First, immunolocalization of ghrelin and NUCB2/<em>nesfatin</em>-<em>1</em> in goldfish hepatopancreas cells was studied by immunohistochemistry. Second, the effects of 2 and 4hour-long exposures of cultured intestine and hepatopancreas sections to glucose, l-tryptophan, oleic acid, linolenic acid (LNA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on ghrelin and <em>nesfatin</em>-<em>1</em> gene and protein expression were studied. Co-localization of ghrelin and NUCB2/<em>nesfatin</em>-<em>1</em> in the cytoplasm of goldfish hepatocytes was found. Exposure to glucose led to an upregulation of preproghrelin and a downregulation of nucb2/<em>nesfatin</em>-<em>1</em> in the intestine. l-Tryptophan mainly decreased the expression of both peptides in the intestine and hepatopancreas. Fatty acids, in general, downregulated NUCB2/<em>nesfatin</em>-<em>1</em> in the intestine, but only the longer and highly unsaturated fatty acids inhibited preproghrelin. EPA exposure led to a decrease in preproghrelin, and an increase in nucb2/<em>nesfatin</em>-<em>1</em> expression in hepatopancreas after 2h. These results show that macronutrients exert a dose- and time-dependent, direct regulation of ghrelin and <em>nesfatin</em>-<em>1</em> in the intestine and hepatopancreas, and suggest a role for these hormones in the digestive process and nutrient metabolism.

The fish heart represents an established natural model for evaluating basic mechanisms of the coordinated physiological reactions which maintain cardiac steady-state. This is due to its relatively simple design, but also to its multilevel morpho-functional flexibility which allows adequate responses to a variety of intrinsic (body size and shape, swimming performance, etc.), and extrinsic (temperature, salinity, oxygen level, water chemistry, etc.) factors related to the animal life style. Nowadays, although many gaps are still present, a huge literature is available about the mechanisms that fine-tune fish cardiac performance, particularly in relation to the influence exerted by substances possessing cardio-modulatory properties. Based on these premises, this review will provide an overview of the existing current knowledge regarding the humoral control of cardiac performance in fish. The role of both classic (i.e. catecholamines, angiotensin II and natriuretic peptides), and emerging cardioactive substances (i.e. the chromogranin-A-derived peptides vasostatins, catestatin and serpinin) will be illustrated and discussed. Moreover, an example of cardiomodulation elicited by peptides (e.g., <em>nesfatin</em>-<em>1</em>) associated to the regulation of feeding and metabolism will be provided. The picture will hopefully emphasize the complex circuits that sustain fish cardiac performance, also highliting the power of the teleost heart as an experimental model to deciphering mechanisms that could be difficult to explore in more elaborated cardiac morpho-functional designs.

BACKGROUND

The mechanisms of fat mass (FM) loss in cystic fibrosis (CF) are poorly understood but could represent complex pathways involving dysregulation of appetite-modulating peptides and an amplified inflammatory response. <em>Nesfatin</em>-<em>1</em> is a newly described peptide that decreases food intake and FM but has not been studied in CF.

OBJECTIVE

We hypothesized that changes in the appetite-suppressing hormone nesfatin-<em>1</em> would be physiological, and levels would be lower in advanced CF patients with lower FM compared to those with milder disease and healthy controls. We determined the levels of the cytokines TNF-α, IL-<em>1</em>β, and IL-6 as they have been associated with weight loss in disease states.

METHODS

Fifty-four adult CF subjects, i.e. <em>1</em>7 with severe, 22 with moderate, and <em>1</em>5 with mild disease, as well as <em>1</em>8 controls were recruited. PFT and body composition analysis (via bioelectrical impedance) were performed. <em>Nesfatin</em>-<em>1</em> and cytokine levels were determined by ELISA.

RESULTS

Contrary to our proposed hypothesis, nesfatin-<em>1</em> levels were highest in CF patients with severe disease and the lowest FM. A significant negative correlation between nesfatin-<em>1</em> levels and FM was found only in the severe CF group (r = -0.7, p = 0.003). In forward stepwise regression analysis, only FM was significantly associated with nesfatin-<em>1</em> levels. Levels of TNF-α and IL-6 were elevated in the severe CF group, but there was no association with either FM or nesfatin-<em>1</em>.

CONCLUSIONS

In advanced CF and low FM, nesfatin-<em>1</em> plasma levels are significantly increased and inversely correlated with the FM. Our results further suggest that nesfatin-<em>1</em> exerts its effects independently of TNF-α or IL-6.

The protein nucleobindin <em>1</em> (NUCB<em>1</em>; also known as CALNUC or Nuc) contains an intriguing combination of DNA- and calcium-binding motifs, a trait that it shares with the protein nucleobindin 2 (NUCB2; also known as <em>nesfatin</em>). NUCB2 has been implicated in several aspects of metabolic control and has been identified in a number of endocrine organs. No such comprehensive mapping of NUCB<em>1</em> has been presented. We have explored the expression and distribution of NUCB<em>1</em> in tissues and cells of the mouse endocrine system, with particular focus on the endocrine pancreas. Using reverse transcription plus the polymerase chain reaction (RT-PCR) and Western blot, we demonstrate that NUCB<em>1</em> is present in the endocrine islets of Langerhans but absent from the exocrine acinar cells. Immunofluorescence studies have revealed that all islet cell types contain NUCB<em>1</em>, including the NUCB2-expressing beta cells. RT-PCR, Western blot and immunofluorescence have shown that NUCB<em>1</em> is expressed in the pituitary, thyroid, parathyroid, gastrointestinal tract, adrenals and gonads. However, within these tissues, NUCB<em>1</em> expression is not ubiquitous. For example, in the testis, NUCB<em>1</em> occurs in the seminiferous tubules but not in the Leydig-cell-containing interstitial tissue. Similarly, the lamina propria of the duodenum lacks NUCB<em>1</em>, despite its presence in enterocytes. Where present, NUCB<em>1</em> consistently appears to be associated with the Golgi apparatus. Thus, NUCB<em>1</em> is broadly, but not ubiquitously, expressed in cells of the mouse endocrine system. Together with its location in the Golgi apparatus and its putative Ca(2+)-binding ability, this distribution suggests a role for NUCB<em>1</em> in Ca(2+) handling/sensing in secretory cells.

Laparoscopic Roux-en-Y gastric bypass (RYGB) achieves a higher remission of type 2 diabetes mellitus (T2DM) than laparoscopic sleeve gastrectomy (SG) in non-morbidly obese patients. However, the mechanisms of the higher remission are unknown. To compare glucagon-provoked acute insulin responses, as well as changes of gut and pancreatic hormones and adipokines between patients with T2DM after RYGB and SG at one year post-operatively, a total of <em>1</em>4 RYGB and <em>1</em>3 SG patients were followed-up and evaluated for glucose metabolism, gut and pancreatic hormones, and adipokines. One year after surgery, <em>1</em>-mg intravenous glucagon tests were performed. The differences in each hormone at different time points and the area under the curve (AUC) were compared between the two groups. Glucagon-stimulated acute insulin responses were not different between the RYGB and SG groups, nor were they different between the remitters and non-remitters at one year after the metabolic surgery. Plasma des-acyl ghrelin and <em>nesfatin</em>-<em>1</em> levels significantly decreased at 6 min after glucagon stimulation in the RYGB and SG groups, as well as in the remitters and non-remitters. The glucagon test did not affect intestinal hormones. Plasma resistin was suppressed after intravenous glucagon stimulation in both RYGB and SG groups. In conclusion, intravenous glucagon inhibited plasma levels of des-acyl ghrelin, <em>nesfatin</em>-<em>1</em>, and resistin in T2DM patients at one year after both RYGB and SG, whereas post-glucagon suppression of plasma obestatin and resistin was shown in the remitters but not in the non-remitters.

BACKGROUND

<em>Nesfatin</em>-<em>1</em> is a newly found anorectic neuropeptide with potent metabolic regulatory effects that its circulating levels are shown to be elevated in diabetes. We compared serum <em>nesfatin</em>-<em>1</em> in patients with type 2 diabetes and microalbuminuria (30mg/day≤urinary albumin excretion (UAE) <300mg/day) with their control patients with type 2 diabetes and normoalbuminuria (UAE <30mg/day).

METHODS

In a cross sectional setting, 44 adult patients with type 2 diabetes and microalbuminuria and 44 control patients with type 2 diabetes and normoalbuminuria were evaluated. Serum levels of <em>nesfatin</em>-<em>1</em> along with demographic, clinical and biochemical factors associated with diabetes was measured.

RESULTS

Mean peripheral concentrations of <em>nesfatin</em>-<em>1</em> were significantly higher in patients with diabetes who had microalbuminuria compared to normoalbuminuric control patients (<em>1</em>75.27±25.96pg/ml vs. <em>1</em>34.66±23.<em>1</em>8pg/ml, respectively; p value<0.00<em>1</em>). Significant positive correlations were found between circulating <em>nesfatin</em>-<em>1</em> levels and the following case-mix variables: duration of diabetes, glycated hemoglobin, plasma creatinine, UAE and serum uric acid. In the multivariate logistic regression and after adjustment for a constellation of potentially confounding variables associated with diabetic kidney disease (DKD), circulating <em>nesfatin</em>-<em>1</em> was the only variable significantly associated with microalbuminuria (odds ratio [95% confidence interval]=<em>1</em>.224 [<em>1</em>.007-<em>1</em>.487], p value=0.042).

CONCLUSIONS

In patients with type 2 diabetes, circulating <em>nesfatin</em>-<em>1</em> appears to be associated with microalbuminuria independent of other established risk factors of DKD. The underlying pathophysiological mechanisms and the prognostic significance of this association remain to be elucidated.

UNASSIGNED

The incidence of depressive symptoms is higher in cancer patients. And depression can also affect the occurrence, development and outcome of cancer through the neuroendocrine-immune-network system.

UNASSIGNED

To study the level of <em>Nesfatin</em>-<em>1</em> in the plasma and brain tissue and its role in the pathogenesis in gastric cancer comorbid with depression using a mouse gastric cancer model.

UNASSIGNED

<em>1</em>8 mice were randomly divided into the normal control group (NCG), gastric cancer without stress model group (GCNS), and gastric cancer combined with stress model group (GCS). The mice of the GCNS group were inoculated subcutaneously with mouse forestomach carcinoma (MFC) after 5 weeks of nomal feeding to establish a model of subcutaneous transplantation tumor. After 5 weeks of chronic unpredicted mild stress (CUMS) in the GCS group, subcutaneous inoculation of MFC was used to establish a subcutaneous transplantation tumor model for <em>1</em> week. Evaluation of mice behavior was performed by open field test, sucrose preference test and forced swimming test (FST). Determination of <em>Nesfatin</em>-<em>1</em> concentration in plasma and brain tissue was carried out using enzyme linked immunosorbent assay (ELISA) and Western Blot.

UNASSIGNED

The weight increment in the GCS group was significantly lower than that in the GCNS group (t=-3.39, p<0.00<em>1</em>). And both GCS and GCNS were lower than the NCG group (t=-6.33, p<0.00<em>1</em>; t=-2.94, p=0.0<em>1</em>). In the open field test, the horizontal moving distance of the GCS group was less than that of the GCNS group (t=-2.50, p=0.025), and both GCS and GCNS were smaller than the NCG group (t=-5.87, p<0.00<em>1</em>; t=-3.38, p=0.004). The dead time of the GCS group was longer than that of the GCNS and the NCG groups (t=2.56, p=0.022; t=3.84, p=0.002). The <em>Nesfatin</em>-<em>1</em> level in the middle brain, hippocampus and plasma was significantly higher in NCG group and GCS group than in the GCNS group. The concentration of <em>Nesfatin</em>-<em>1</em> in the GCS group was significantly higher than that in the NCG group.

UNASSIGNED

There is a decrease of <em>Nesfatin</em>-<em>1</em> level in brain tissue and plasma in mice with gastric cancer without stress. CUMS stress can induce depressive behavior in gastric cancer mice, and increase the level of <em>Nesfatin</em>-<em>1</em> in brain tissue and plasma. Therefore, <em>Nesfatin</em>-<em>1</em> may be related to the pathogenesis of gastric cancer stress related depression.

OBJECTIVE

Ischemia causes reversible or irreversible cell or tissue damage and reperfusion can exaggerate cellular damage. Microvascular dysfunction is induced and causes enhanced fluid filtration in capillaries. At the acute phase of reperfusion more oxygen radicals are activated. <em>Nesfatin</em>-<em>1</em> protects brain against oxidative damage and heart against ischemia/reperfusion damage. In our study, we aimed to investigate the acute effect of chronic peripheral <em>nesfatin</em>-<em>1</em> administration in intestinal ischemia/reperfusion created rats.

METHODS

Two-months-old, 28 Wistar Albino male rats, weighing an average of 200-250 g, were used and randomly divided into four experimental groups (n=7) as; Laparotomy, Ischemia/Reperfusion, <em>Nesfatin</em>-<em>1</em>+Laparotomy, <em>Nesfatin</em>-<em>1</em>+Ischemia/Reperfusion. Serum levels of total oxidant status (TOS) and total antioxidant status (TAS) were determined by colorimetric measurement method. The plasma levels of endotelin-<em>1</em> and endothelial nitric oxide syntheses (eNOS) were analyzed by rat ELISA assay kits.

RESULTS

Plasma levels of endothelin-<em>1</em> significantly increased, plasma level of eNOS, serum levels of TOS and TAS significantly decreased in <em>nesfatin</em>-<em>1</em> applied groups. Additionally, The oxidative stress index (OSI) parameters decreased significantly in three groups compared to laparotomy.

CONCLUSIONS

Chronic peripheral <em>nesfatin</em>-<em>1</em> administration can decrease eNOS level and OSI at the acute phase of ischemia/reperfusion. We suppose that it can be protective for ischemia/reperfusion injury by balancing oxidant capacity. On the other hand, this effect of <em>nesfatin</em>-<em>1</em> is not related with micro-circular compensation and increases anti-oxidant capacity.

BACKGROUND

<em>Nesfatin</em>-<em>1</em> is an anorexigenic hormone suggested to regulate obesity.

OBJECTIVE

To investigate the relationship between nesfatin-<em>1</em> level and anthropometric and metabolic parameters in obese patients, and examine the change in plasma nesfatin-<em>1</em> level after acupuncture treatment.

METHODS

64 obese adult patients without diabetes and 58 normal weight control subjects were enrolled in this study. The obese patients were randomly divided into an acupuncture plus diet group (n=32) and a diet only group (n=32). Measurements were repeated after 45 days.

RESULTS

Body mass index (BMI), waist and hip circumferences, serum insulin, lipoprotein and insulin resistance measures were significantly higher, and plasma nesfatin-<em>1</em> level was significantly lower, in obese patients than in normal weight controls. In addition, negative correlations were found between plasma nesfatin-<em>1</em> level and BMI, waist and hip circumferences. Weight reduction in participants after acupuncture and diet restriction was 7.0% and 4.3%, respectively. Plasma nesfatin-<em>1</em> level increased from 2.75±<em>1</em>.<em>1</em>6 to 3.44±<em>1</em>.28 ng/mL and from 2.86±<em>1</em>.07 to 3.23±<em>1</em>.06 ng/mL in acupuncture and diet groups, respectively; the difference was significant, p<0.05.

CONCLUSIONS

Plasma nesfatin-<em>1</em> level is reduced in obese adults, and is increased after acupuncture. The beneficial effect of acupuncture on obesity is associated with increased plasma nesfatin-<em>1</em> level.

<em>Nesfatin</em>-<em>1</em> is an 82 amino acid peptide that inhibits food intake in rodents and fish. While endogenous <em>nesfatin</em>-<em>1</em>, and its role in the regulation of food intake and hormone secretion has been reported in fish, information on cardiovascular functions of <em>nesfatin</em>-<em>1</em> in fish is in its infancy. We hypothesized that cardiac NUCB2 expression is meal responsive and <em>nesfatin</em>-<em>1</em> is a cardioregulatory peptide in zebrafish. NUCB2/<em>nesfatin</em>-<em>1</em> like immunoreactivity was detected in zebrafish cardiomyocytes. Real-time quantitative PCR analysis found that the cardiac expression of NUCB2A mRNA in unfed fish decreased at <em>1</em>h post-regular feeding time. Food deprivation for 7days did not change NUCB2A mRNA expression. However, NUCB2B mRNA expression was increased in the heart of zebrafish after a 7-day food deprivation. Ultrasonography of zebrafish heart at <em>1</em>5min post-intraperitoneal injection of <em>nesfatin</em>-<em>1</em> (250 and 500ng/g body weight) showed a dose-dependent inhibition of end diastolic and end systolic volumes. A dose dependent decrease in heart rate and cardiac output was observed in zebrafish that received <em>nesfatin</em>-<em>1</em>, but no changes in stroke volume were found. <em>Nesfatin</em>-<em>1</em> treatment caused a significant increase in the expression of Atp2a2a mRNA encoding the calcium-handling pump, SERCA2a, while it had no effects on the expression of calcium handling protein RyR<em>1</em>b encoding mRNA. Our data support cardiosuppressive effects of <em>nesfatin</em>-<em>1</em> in zebrafish, and reveals energy availability as one determinant of cardiac NUCB2 mRNA expression.

<em>Nesfatin</em>-<em>1</em>, an 82-amino acid neuropeptide, has been shown to induce anorexia and energy expenditure. Food intake is decreased in ad libitum-fed rats following injections of <em>nesfatin</em>-<em>1</em> into the lateral, third, or fourth ventricles of the brain. Although the lateral parabrachial nucleus (LPBN) is a key regulator of feeding behavior and thermogenesis, the role of <em>nesfatin</em>-<em>1</em> in this structure has not yet been delineated. We found that intra-LPBN microinjections of <em>nesfatin</em>-<em>1</em> significantly reduced nocturnal cumulative food intake and average meal sizes without affecting meal numbers in rats. Because glucose sensitive neurons are involved in glucoprivic feeding and glucose homeostasis, we examined the effect of <em>nesfatin</em>-<em>1</em> on the excitability of LPBN glucosensing neurons. In vivo electrophysiological recordings from LPBN glucose sensitive neurons showed that <em>nesfatin</em>-<em>1</em> (<em>1</em>.5 × <em>1</em>0-8 M) excited most of the glucose-inhibited neurons. Chronic administration of <em>nesfatin</em>-<em>1</em> into the LPBN of rats reduced body weight gain and enhanced the expression of uncoupling protein <em>1</em> (UCP<em>1</em>) in brown adipose tissue (BAT) over a <em>1</em>0-day period. Furthermore, the effects of <em>nesfatin</em>-<em>1</em> on food intake, body weight, and BAT were attenuated by treatment with the melanocortin antagonist SHU9<em>1</em><em>1</em>9. These results demonstrate that <em>nesfatin</em>-<em>1</em> in LPBN inhibited food intake, modulated excitability of glucosensing neurons and enhanced UCP<em>1</em> expression in BAT via the melanocortin system.

<em>Nesfatin</em>-<em>1</em> is a recently identified anorexigenic hypothalamic polypeptide derived from the posttranslational processing of nucleobindin 2 (NUCB2). Several studies have indicated that this neuropeptide may be participated in somatosensory and visceral transmission including pain signals in addition to energy metabolism. The aim of this study was to explore the possible role of <em>nesfatin</em>-<em>1</em> in the transmission of peripheral neural signals by investigating the effects of <em>nesfatin</em>-<em>1</em> on intracellular free calcium levels ([Ca(2+)]i) in cultured neonatal rat dorsal root ganglion (DRG) neurons. The effects of <em>nesfatin</em>-<em>1</em> on [Ca(2+)]i in DRG neurons were investigated by using an in vitro calcium imaging system. DRG neurons were grown in primary culture following enzymatic and mechanical dissociation of ganglia from <em>1</em>-or 2-day-old neonatal Wistar rats. Using the fura-2-based calcium imaging technique, the effects of <em>nesfatin</em>-<em>1</em> on [Ca(2+)]i and role of the protein kinase C (PKC)-mediated pathway in <em>nesfatin</em>-<em>1</em> effect were assessed. <em>Nesfatin</em>-<em>1</em> elevated [Ca(2+)]i in cultured DRG neurons. The response was prevented by pretreating the cells with pertussis toxin. The protein kinase C inhibitor chelerythrine chloride suppressed <em>nesfatin</em>-<em>1</em>-induced rise in [Ca(2+)]i. The result shows that <em>nesfatin</em>-<em>1</em> interacts with a G protein-coupled receptor, leading to an increase of [Ca(2+)]i, which is linked to protein kinase C activation in cultured rat DRG neurons.

The anorexigenic molecule <em>nesfatin</em>-<em>1</em> has recently been taken as a potential mood regulator, but the potential mechanisms remain unknown. Results of our previous study have demonstrated that <em>nesfatin</em>-<em>1</em> could induce anxiety- and depression-like behaviors in rats, accompanied by the hyperactivity of the hypothalamic-pituitary-adrenal axis and the imbalanced mRNA expression of synaptic vesicle proteins. To explore the potential neurobiological mechanism underlying the effect of <em>nesfatin</em>-<em>1</em> on the synaptic plasticity, the human neuroblastoma SH-SY5Y cells were cultured and treated with different concentrations of <em>nesfatin</em>-<em>1</em> in the present study. The mRNA and protein expressions of corticotropin-releasing hormone (CRH) were measured via real-time fluorescent quantitative PCR and western blot, respectively. The protein expressions of extracellular signal-regulated kinase <em>1</em>/2 (ERK<em>1</em>/2), phosphorylated-ERK<em>1</em>/2 (p-ERK<em>1</em>/2), and synapsin I were detected via western blot. The results confirmed that <em>nesfatin</em>-<em>1</em> (<em>1</em>0-9~<em>1</em>0-7 mol/L) could up-regulate the expression of CRH. Moreover, <em>nesfatin</em>-<em>1</em> (<em>1</em>0-9~<em>1</em>0-7 mol/L) could also increase the protein expressions of p-ERK<em>1</em>/2 and synapsin I, and these effects could be blocked by CP376395, a selective antagonist of CRH type <em>1</em> receptor (CRHR<em>1</em>). Furthermore, the increased expression of synapsin I induced by <em>nesfatin</em>-<em>1</em> could also be reversed by PD98059, a specific inhibitor of the p-ERK. These results indicated that CRHR<em>1</em> might mediate the effect of <em>nesfatin</em>-<em>1</em> on the expressions of synapsin I via ERK<em>1</em>/2 signaling pathway.

In this study, we report <em>nesfatin</em>-<em>1</em> immunoreactivity in the gastrointestinal tract of Casertana breed pig. The newly discovered anorexigenic peptide <em>nesfatin</em>-<em>1</em> has been shown to possess physiological relevance in regulating food intake and energy homeostasis at a central level, although evidence has been accumulating that it may also play important functions at a more local gastroenteric level. <em>Nesfatin</em>-<em>1</em> immunoreactive endocrine cells have been detected in the gastric fundus and ileocecal valve. <em>Nesfatin</em>-<em>1</em> immunopositive neurons and nerve fibers have been observed mainly in the enteric plexuses. Western blot analysis confirmed the immunohistochemical observations, showing immunoreactive bands in all analyzed gastrointestinal tracts with the exception of the rectum. <em>Nesfatin</em>-<em>1</em> immunodetection in the swine digestive system reinforces the importance of the role played by <em>nesfatin</em>-<em>1</em> at the gastrointestinal level and sustains the necessity to study the role of this peptide in the regulation of food intake in farm species for which weight gain is essential for optimizing production.

BACKGROUND

Anemia is a disease that is long and often repetitive and can result in a great burden to the national economy. The most frequent nutritional deficiency anemias in children are related with iron and vitamin B<em>1</em>2 deficiencies.

OBJECTIVE

The aim of this study was to determine the oxidative stress, hepcidin, and <em>nesfatin</em>-I levels in childhood iron and vitamin B<em>1</em>2 deficiency anemias.

METHODS

The study had 3 groups of <em>1</em>5 children, iron anemia deficiency group, vitamin B<em>1</em>2 deficiency group and a control group.

RESULTS

The TBARS and <em>nesfatin</em>-I levels were significantly higher in the iron and vitamin B<em>1</em>2 deficiency groups and the total antioxidant levels were significantly lower when compared to the control group. In contrast, the plasma hepcidin levels were significantly lower in the iron deficiency group (p < 0.0<em>1</em>) when compared to the control group; however, no significant differences were observed in the vitamin B<em>1</em>2 deficiency group. Plasma homocysteine levels were significantly higher in the vitamin B<em>1</em>2 deficiency group when compared to the control group (p < 0.00<em>1</em>), but no differences were determined between the iron deficiency and control groups.

CONCLUSIONS

Our results showed that there are high levels of oxidative stress in childhood iron and vitamin B<em>1</em>2 deficiency anemias, and we propose that plasma hepcidin and homocycteine levels may be useful in the differential diagnosis of childhood nutritional deficiency anemias. <em>Nesfatin</em>-<em>1</em> hormone levels were identified for the first time in childhood iron deficiency and vitamin B<em>1</em>2 deficiency anemias within this study and this hormone may also be useful in the differential diagnosis of anemias.

OBJECTIVE

Levels of the hormones ghrelin and leptin in rat models of acute pancreatitis (AP) have been investigated in several experimental studies. However, there are very few clinical studies addressing the connection between hormone levels and AP. A few recent studies investigating the changes in ghrelin and leptin levels in patients with AP have been reported; however, our study is the first clinical study to investigate the change of <em>nesfatin</em>-<em>1</em> levels in patients with gallstone-induced AP.

METHODS

Forty patients were enrolled in this study, eight of which presented with severe AP. Two blood samples were obtained from each study patient. The first blood samples were obtained at patient admission to the hospital and the second was obtained at patient discharge. All samples were collected after at least 6 h of fasting. Plasma <em>nesfatin</em>-<em>1</em>, leptin, and ghrelin levels were measured.

RESULTS

In all 40 patients, <em>nesfatin</em>-<em>1</em> and leptin levels were higher at admission and had decreased at discharge. In contrast, the ghrelin levels at discharge were significantly higher than those at admission. Only the changes in these hormones in the mild AP group were significant.

CONCLUSIONS

Levels of these hormones were altered during the course of gallstone-induced AP. These changes might be associated with the clinical outcomes of the disease. To clarify whether the magnitude of the change in hormone levels at AP onset can be used as a biomarkers to predict the severity of the disease requires further investigation.

BACKGROUND

<em>Nesfatin</em>-<em>1</em> was originally identified as a neuropeptide of the hypothalamus, which is a key integration area of the brain, where numerous neuropeptides and transmitters are released to participate in the control of essential body functions. In the literature, there are no studies showing the relationship between the <em>nesfatin</em>-<em>1</em> level and paroxysmal supraventricular tachycardia. We hypothesize that the circulating levels of <em>nesfatin</em>-<em>1</em> may increase during supraventricular tachycardia, to engage the vagal stimulation to terminate by the inhibition of neuropeptide-Y, and may activate oxytocin and the corticotropin-releasing hormone.

METHODS

This study includes <em>1</em>20 cases (80 patients and 40 controls). Patients with paroxysmal supraventricular tachycardia were compared with the control group with regard to sex, <em>nesfatin</em>-<em>1</em> level, comorbid diseases, serum renal function values, and patients' vital findings.

RESULTS

The <em>nesfatin</em>-<em>1</em> levels were significantly higher in the paroxysmal supraventricular tachycardia group than in the control group and positively correlated highly with heart rate (r = 0.634; P < 0.00<em>1</em>). The area under the receiver operating characteristic curve was 0.644 for the <em>nesfatin</em>-<em>1</em> levels (P = 0.005<em>1</em>). The sensitivity and specificity values of the <em>nesfatin</em>-<em>1</em> levels were 4<em>1</em>.2% and 95%, respectively (cutoff value>><em>1</em>743.7 pg/mL).

CONCLUSIONS

At the end of this study, a statistically significant correlation was found between the serum <em>nesfatin</em>-<em>1</em> level and supraventricular tachycardia. Although multifactorial causes may explain the relationship, we based our hypothesis on the relationship of the antagonistic effects of <em>nesfatin</em>-<em>1</em> on the neuropeptide-Y and activated oxytocin.

<em>Nesfatin</em>-<em>1</em>, an 82 amino acid peptide was discovered in 2006 in the rat hypothalamus and described as a centrally acting anorexigenic peptide. Besides its central expression and actions, NUCB2/<em>nesfatin</em>-<em>1</em> has been subsequently described to be predominantly expressed in the periphery and to exert several peripheral effects. The current review focuses on the expression sites of NUCB2/<em>nesfatin</em>-<em>1</em> in peripheral tissues of different species and its regulation by nutrition, body weight and various other parameters such as fetal development and sex.