Nesfatin-1 is the N-terminal fragment of nucleobindin-2 (NUCB2). The antibody against nesfatin-1 recognizes both full length of NUCB2 and nesfatin-1, thus the immunolabeling represents ...NUCB2/nesfatin-1. It has been found that NUCB2/nesfatin-1 is widely distributed in the rodent central nervous system. The immunoreactivity is more intensive in the brain autonomic centers that regulate feeding, neuroendocrine and cardiovascular functions, such as the hypothalamic paraventricular nucleus, supraoptic nucleus, lateral hypothalamic area, Edinger-Westphal nucleus, locus coeruleus, dorsal vagal complex and medullary raphe nuclei. In neurons, NUCB2/nesfatin-1 is located in the soma and primary dendrites, not in nerve fibers. NUCB2/nesfatin-1 is co-localized with several neurotransmitters involved in regulation of food intake, autonomic and neuroendocrine functions, including oxytocin, vasopressin, neuropeptide Y, cocaine- and amphetamine-regulated transcript, proopiomelanocortin, α-melanocyte-stimulating hormone, melanin-concentrating hormone, leptin, mammalian target of rapamycin, urocortin-1, corticotropin-releasing factor and serotonin. In the periphery, NUCB2/nesfatin-1 is located mainly in the pituitary, gastric mucosa where it coexists with ghrelin, and pancreatic endocrine cells containing insulin. Nesfatin-1 is detectable in the cerebrospinal fluid of rats. NUCB2/nesfatin-1 is measurable in the plasma, and altered under different conditions in rodents and humans, such as immune challenge, high fat diet and exercise, anorexia nervosa, anxiety and depression. Anatomical data suggest that nesfatin-1 is a unique neuroendocrine peptide that may be involved in regulation of homeostasis.
Abstract Nesfatin-1 reduces food intake when injected centrally in rodents. We recently described wide distribution of nucleobindin2 (NUCB2)/nesfatin-1 immunoreactivity in rat brain autonomic nuclei ...activated by various stressors. We used C57BL/6 mice to localize brain NUCB2/nesfatin-1 immunoreactivity and assessed activation of NUCB2/nesfatin 1 neurons after water avoidance stress (WAS). Gastric emptying of a non-nutrient liquid was also determined. NUCB2/nesfatin-1 immunoreactivity was detected in cortical areas including piriform, insular, cingulate and somatomotor cortices, the limbic system including amygdaloid nuclei, hippocampus and septum, the basal ganglia, bed nucleus of the stria terminalis, the thalamus including paraventricular and parafascicular nuclei, the hypothalamus including supraoptic, periventricular, paraventricular (PVN), arcuate nuclei and ventromedial and lateral hypothalamic areas. Intensely labeled NUCB2/nesfatin-1 neurons were detected in a previously undefined region which we named intermediate dorsomedial hypothalamus. In the brainstem, NUCB2/nesfatin-1 immunoreactivity was detected in the raphe nuclei, Edinger–Westphal nucleus, locus coeruleus (LC), lateral parabrachial nucleus, ventrolateral medulla (VLM) and dorsal vagal complex. WAS induced Fos expression in 35% of NUCB2/nesfatin-1-immunoreactive neurons in the PVN, 50% in the LC, 54% in the rostral raphe pallidus, 58% in the VLM, 39% in the middle part of the nucleus of the solitary tract (NTS) and 33% in the caudal NTS. Nesfatin-1 injected intracerebroventricularly significantly decreased gastric emptying. These data showed that NUCB2/nesfatin-1 immunoreactivity is distributed in mouse brain areas involved in the regulation of stress response and visceral functions activated by an acute psychological stressor suggesting that nesfatin-1 might play a role in the efferent component of the stress response.
Nesfatin-1 was recently identified and introduced as food intake-regulatory hormone. Soon thereafter, mounting evidence indicated a much broader role for nesfatin-1 with an involvement in the ...regulation of food intake, gastrointestinal motility, glucose homeostasis, blood pressure and stress. Despite the growing knowledge on the physiological regulation and functions of nesfatin-1, the receptor mediating these effects remains to be characterized. Therefore, the aim of this study was to investigate the peripheral and central localization of the nesfatin-1 receptor by autoradiography. Male Sprague–Dawley rats were used and peripheral as well as brain tissue was processed for 125I-nesfatin-1 autoradiography. In peripheral tissues, an autoradiographic signal was observed in the gastric mucosa of corpus and antrum, in duodenum, jejunum and ileum, while no signal was detected in the colon. Preabsorption of 125I-nesfatin-1 with non-labeled nesfatin-1 greatly diminished the autoradiographic signal in the stomach indicating specificity (−32%, p < 0.001). A displacement assay showed an effective concentration by which 50% of 125I-nesfatin-1 bound to the receptor (EC50) in the gastric corpus of 80 pM. Moreover, autoradiography was observed in endocrine tissues including the pituitary, pancreas, adrenal gland, testis and visceral adipose tissue. In addition, also heart, skeletal muscle, lung, liver and kidney showed autoradiographic signals. In the brain, strong 125I-nesfatin-1 autoradiography was detected in the cortex, paraventricular nucleus of the hypothalamus, area postrema, dorsal motor nucleus of the vagus nerve and cerebellum. Based on the distribution of nesfatin-1 autoradiography, nesfatin-1 is a pleiotropic hormone that is involved in the regulation of several homeostatic functions.
•Although our knowledge on nesfatin-1 is increasing, the receptor is still unknown.•125I-nesfatin-1 autoradiography was detected in (a.o.) the stomach and pancreas.•Central signals were observed in the hypothalamic paraventricular and dorsal motor nucleus.•Distribution data support the notion of nesfatin-1 being a pleiotropic hormone.
Phoenixin is a pleiotropic peptide involved in reproduction, anxiety and recently also implicated in the control of food intake. Besides the 20-amino acid phoenixin, the 14-amino acid phoenixin-14 ...also shows bioactive properties. However, the expression sites of phoenixin-14 in the brain and peripheral tissues are not yet described in detail. Therefore, a mapping of the brain and peripheral tissues from male and female Sprague-Dawley rats with a specific phoenixin-14 antibody was performed using western blot and immunohistochemistry. High density of phoenixin-14 immunoreactivity was detected in the medial division of the brain central amygdaloid nucleus, in the spinal trigeminal tract and in the spinocerebellar tract as well as in cells between the crypts of duodenum, jejunum and ileum. Medium density immunoreactivity was observed in the bed nucleus of the stria terminalis, in the area postrema, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve as well as in the peripheral parts of the islets of Langerhans in the pancreas. A low density of phoenixin-14 immunoreactivity was detected in the arcuate nucleus, the supraoptic nucleus and the raphe pallidus. After pre-absorption of the antibody with phoenixin-14 peptide, no immunosignals were observed indicating specificity of the antibody. Taken together, the widespread distribution of phoenixin-14 immunoreactivity gives additional rise to the pleiotropic functions of the peptide such as possible effects in gastrointestinal motility, immune functions and glucose homeostasis.
•Phoenixin-14 immunoreactivity was detected in distinct nuclei of forebrain.•Phoenixin-14 immunoreactivity was observed in hindbrain and spinal cord.•Phoenixin-14 immunoreactivity was detected in small intestine and endocrine pancreas.•Widespread immunoreactivity gives rise to pleiotropic functions of phoenixin-14.
The unpredictable nature of peptide binding to surfaces requires optimization of experimental containers to be used. To demonstrate the variable recoveries of peptides from multiple surfaces commonly ...employed in peptide research, we tested the recovery of radiolabeled
125I endocrine peptides under different conditions and provide guidelines for determining the surfaces to use for other peptides.
125I-labeled peptides (ghrelin, sulfated cholecystokinin-8, corticotropin-releasing factor, glucagon-like peptide-1 GLP-1, insulin, leptin, nesfatin-1, and peptide YY), representing a wide spectrum in net charge, size, end group, and modification, were incubated for 48
h in glass and plastic tubes untreated or coated with siliconizing fluid. Best surfaces were chosen and peptides were incubated with bovine serum albumin (BSA, 1%) with or without subsequent lyophilization. Recovery of
125I-labeled peptides was determined by gamma counting. Important differences in
125I-labeled peptide binding capacities to various types of surfaces exist. Siliconization decreased, whereas the addition of BSA improved recovery from surfaces tested. Lyophilizing solutions containing
125I-labeled peptides and BSA in the tubes best suited for individual peptides rendered more than 89% recovery for all peptides. Ghrelin specifically displaced
125I-ghrelin from borosilicate glass, whereas GLP-1 and Fmoc-arginine did not. Choosing the appropriate experimental container avoids unpredictable peptide loss that results in inaccurate measurements and false conclusions.
Kisspeptin is distributed not only in brain areas for regulating reproduction but also in nuclei involved in feeding control. Whether kisspeptin alters food intake is unknown in mice. We examined how ...kisspeptin-10 influences feeding after intracerebroventricular injection in mice using automated monitoring. Kisspeptin-10 (0.3, 1, and 3 μg/mouse) dose-dependently inhibited the feeding response to an overnight fast by 50, 95, and 90% respectively, during the 2-3 h period postinjection. The 1μg/mouse dose reduced the 4-h cumulative food intake by 28% whereas intraperitoneal injection (10 μg/mouse) did not. The decreased 4-h food intake was due to reduced meal frequency (-45%/4 h), whereas meal size and gastric emptying were not altered. These data suggest that kisspeptin may be a negative central regulator of feeding by increasing satiety.
Functional gastrointestinal disorders are frequent diseases often associated with a pronounced burden reflected in a greatly reduced quality of life. Patients are seeking medical help but may be ...perceived as demanding and challenging. For successful diagnosis and treatment of these patients, a good doctor-patient communication is key. However, so far, only few studies focus on the physicians’ perspective of the doctor-patient communication. The present study cross-sectionally investigated 520 physicians using the validated difficult doctor-patient relationship questionnaire and the treatment satisfaction questionnaire from the physician’s perspective along with several
ad hoc
questions. Data from 5,354 physician-patient conversations (one conversation per patient) was included. Physicians participating in this study mostly suspected stress-related burdens as the cause of functional gastrointestinal disorders (65.4%), while patients rather suspected food (55.4%) or other somatic causes (43.6%). The physician-patient relationship was rated just below the threshold for difficult interactions (cut-off ≥30, mean ± SD in the current sample: 28.6 ± 9.6) with 49.1% of physicians reaching a score of ≥30. Although physicians overall felt confident in the doctor-patient communication even in difficult conversations (61.9%), only 33.1% reported to have enough time for these patients and only 5.6% felt sufficiently compensated for discussions with patients with functional gastrointestinal disorders. Therefore, education of physicians on functional gastrointestinal disorders, training of physicians in physician-patient communication as well as an improved reimbursement of speaking medicine should help to further improve care for these patients and also treatment satisfaction on both the side of the patients as well as the physicians.
Background: Nucleobindin2 (NUCB2)/nesfatin-1 plays a well-established
role in homeostatic functions associated with food intake and stress integration.
Aim: This review focusses on NUCB2/nesfatin-1's ...central effects on gastrointestinal
functions and will summarize the effects on food intake, motility and secretion with
focus on the upper gastrointestinal tract.
Results: We will highlight the stressors that influence brain NUCB2/nesfatin-1 expression
and discuss functional implications. In addition to traditional acute psychological and
physical stressors such as restraint stress and abdominal surgery we will look at
immunological, visceral and metabolic stressors as well as a chronic combination
stress model that have been shown to affect NUCB2/nesfatin-1 signaling and describe associated
functional consequences.
Gastrointestinal (GI) complaints are frequently observed in patients who suffer from anorexia nervosa (AN). These symptoms may hamper treatment and weight regain and are often perceived as the cause, ...not the consequence, of the disease. Since carbohydrate malabsorption also produces these symptoms, this might underly or contribute to these complaints. So far, the role of carbohydrate malabsorption (fructose malabsorption and lactose intolerance) in AN has not yet been investigated.
For this case series, inpatients with AN of restrictive type (
= 3), purging type (
= 3), and atypical AN (
= 1) conducted hydrogen breath tests with 25 g of fructose and 50 g of lactose to investigate carbohydrate malabsorption. Results were then analyzed in association with body mass index (BMI) and patient-reported outcomes (disordered eating, body image disturbances, anxiety, depressive symptoms, perceived stress, and GI complaints).
Based on the hydrogen breath test results, three of the seven female patients were classified as lactose intolerant and one presented fructose malabsorption. Both hydrogen curves for fructose (
= -0.632,
< 0.001) and lactose (
= -0.704,
< 0.001) showed a negative correlation with BMI. No association was observed between hydrogen values and patient-reported outcomes.
In patients with AN, GI symptoms caused by intolerance of common monosaccharides and disaccharides may be an underestimated burden and should be considered in the diagnosis and therapy of patients with AN. Due to the observed correlation with BMI, GI complaints after ingestion of fructose or lactose likely develop with decreasing body weight and are potentially reversible with weight regain.
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