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Book ; Online ; Thesis: Untersuchung zur zentralen Appetitregulation durch die Neuropeptide Ghrelin, desacyl-Ghrelin und Obestatin

2010

Author's details	Anna-Sophia Wisser
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Medizinische Fakultät Charité - Universitätsmedizin Berlin
Publishing place	Berlin
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Interactions of Gastrointestinal Peptides

Anna-Sophia Wisser / Piet Habbel / Bertram Wiedenmann / Burghard F. Klapp / Hubert Mönnikes / Peter Kobelt

International Journal of Peptides, Vol

Ghrelin and Its Anorexigenic Antagonists

2010 Volume 2010

Keywords	Biochemistry ; QD415-436 ; Organic chemistry ; QD241-441 ; Chemistry ; QD1-999 ; Science ; Q ; DOAJ:Biochemistry ; DOAJ:Life Sciences ; DOAJ:Biology and Life Sciences
Language	English
Publishing date	2010-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interactions of gastrointestinal peptides: ghrelin and its anorexigenic antagonists.

Wisser, Anna-Sophia / Habbel, Piet / Wiedenmann, Bertram / Klapp, Burghard F / Mönnikes, Hubert / Kobelt, Peter

International journal of peptides

2010 Volume 2010

Abstract: Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates ... ...

Abstract	Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK), bombesin, desacyl ghrelin, peptide YY (PYY), as well as glucagon-like peptide (GLP). Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite.
Language	English
Publishing date	2010-01-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2570929-X
ISSN	1687-9775 ; 1687-9767
ISSN (online)	1687-9775
ISSN	1687-9767
DOI	10.1155/2010/817457
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Somatic comorbidities of irritable bowel syndrome: a systematic analysis.

Riedl, Andrea / Schmidtmann, Marco / Stengel, Andreas / Goebel, Miriam / Wisser, Anna-Sophia / Klapp, Burghard F / Mönnikes, Hubert

Journal of psychosomatic research

2008 Volume 64, Issue 6, Page(s) 573–582

Abstract: Objective: A large number of irritable bowel syndrome (IBS) patients are additionally afflicted with other somatic intestinal and/or extraintestinal comorbidities. The occurrence of one or more comorbidities is correlated with enhanced medical help ... ...

Abstract	Objective: A large number of irritable bowel syndrome (IBS) patients are additionally afflicted with other somatic intestinal and/or extraintestinal comorbidities. The occurrence of one or more comorbidities is correlated with enhanced medical help seeking, worse prognosis, and higher rates of anxiety and depression-all resulting in a reduced quality of life. The aims of this study were, firstly, to review the literature on comorbidities of IBS and to assess gastrointestinal and extraintestinal comorbidities, and, secondly, to evaluate explanatory hypotheses and possible common pathophysiological mechanisms. Methods: We systematically reviewed the scientific literature in the past 25 years, as cited in MEDLINE. Results: IBS patients present with a twofold increase in somatic comorbidities compared to controls, possibly caused by common pathophysiological mechanisms. Nevertheless, to date, there has been no convincing evidence for a consolidated underlying pathophysiology or somatization. Gastrointestinal disorders, such as functional dyspepsia, gastroesophageal reflux disease, functional constipation, and anal incontinence, occur in almost half of the patients. In a broad variety of extraintestinal comorbidities, fibromyalgia, chronic fatigue syndrome, and chronic pelvic pain are best documented and appear in up to 65%. Conclusion: The knowledge and structured assessment of comorbid somatic symptoms might allow to identify subgroups of IBS patients with special characteristics and lead to adaptation of the therapeutic concept.
MeSH term(s)	Comorbidity ; Diagnosis, Differential ; Fatigue Syndrome, Chronic/diagnosis ; Fatigue Syndrome, Chronic/epidemiology ; Female ; Female Urogenital Diseases/diagnosis ; Female Urogenital Diseases/epidemiology ; Humans ; Irritable Bowel Syndrome/diagnosis ; Irritable Bowel Syndrome/epidemiology ; Male ; Male Urogenital Diseases/diagnosis ; Male Urogenital Diseases/epidemiology ; Migraine Disorders/diagnosis ; Migraine Disorders/epidemiology ; Musculoskeletal Diseases/diagnosis ; Musculoskeletal Diseases/epidemiology ; Pain/diagnosis ; Pain/epidemiology ; Somatoform Disorders/diagnosis ; Somatoform Disorders/epidemiology ; Somatoform Disorders/psychology
Language	English
Publishing date	2008-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80166-5
ISSN	1879-1360 ; 0022-3999
ISSN (online)	1879-1360
ISSN	0022-3999
DOI	10.1016/j.jpsychores.2008.02.021
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Article ; Online: CCK-8S activates c-Fos in a dose-dependent manner in nesfatin-1 immunoreactive neurons in the paraventricular nucleus of the hypothalamus and in the nucleus of the solitary tract of the brainstem.

Noetzel, Steffen / Stengel, Andreas / Inhoff, Tobias / Goebel, Miriam / Wisser, Anna-Sophia / Bannert, Norbert / Wiedenmann, Bertram / Klapp, Burghard F / Taché, Yvette / Mönnikes, Hubert / Kobelt, Peter

Regulatory peptides

2009 Volume 157, Issue 1-3, Page(s) 84–91

Abstract: Recently, a new neuropeptide, named nesfatin-1, was discovered. It has been reported that nesfatin-1 inhibits food intake after injection into the third ventricle as well as intraperitoneal (ip) injection. Cholecystokinin (CCK) is well established to ... ...

Abstract	Recently, a new neuropeptide, named nesfatin-1, was discovered. It has been reported that nesfatin-1 inhibits food intake after injection into the third ventricle as well as intraperitoneal (ip) injection. Cholecystokinin (CCK) is well established to play a role in the regulation of food intake. The aim of the study was to examine whether CCK-8S injected ip modulates neuronal activity in nesfatin-1 immunoreactive (ir) neurons localized in the PVN and in the nucleus of the solitary tract (NTS). Additionally, tyrosine hydroxylase-immunoreactivity (TH-ir) in the PVN was determined to assess the distribution of TH-ir fibers in relation to nesfatin-1-ir. Non-fasted male Sprague-Dawley rats received 6 or 10 microg CCK-8S/kg or vehicle solution (0.15M NaCl; n=4 all groups) ip. The number of c-Fos-ir neurons was determined in the PVN, arcuate nucleus (ARC), and NTS. Double staining procedure for nesfatin-1 and c-Fos revealed that CCK-8S increased significantly and in a dose-dependent manner the number of c-Fos positive nesfatin-1-ir neurons in the PVN ( approximately 4-fold and approximately 7-fold) and NTS ( approximately 9-fold and approximately 26-fold). Triple staining in the PVN showed a dose-dependent neuronal activation of nesfatin-1 neurons that were colocalized with CRF and oxytocin. Double labeling against nesfatin-1 and TH revealed that nefatin-1-ir neurons were encircled in a network of TH-ir fibers in the PVN. No effect on the number of c-Fos-ir neurons was observed in the ARC. These results suggest that the effects of CCK on the HPA axis and on food intake may, at least in part, be mediated by nesfatin-1-ir neurons in the PVN.
MeSH term(s)	Animals ; Brain Stem/cytology ; Brain Stem/metabolism ; Calcium-Binding Proteins ; DNA-Binding Proteins ; Dose-Response Relationship, Drug ; Injections, Intraperitoneal ; Male ; Nerve Tissue Proteins/metabolism ; Neurons/drug effects ; Neurons/immunology ; Paraventricular Hypothalamic Nucleus/cytology ; Paraventricular Hypothalamic Nucleus/metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley ; Sincalide/administration & dosage ; Sincalide/analogs & derivatives ; Sincalide/pharmacology
Chemical Substances	8-sulfocholecystokinin octapeptide ; Calcium-Binding Proteins ; DNA-Binding Proteins ; Nerve Tissue Proteins ; Proto-Oncogene Proteins c-fos ; nucleobindin ; Sincalide (M03GIQ7Z6P)
Language	English
Publishing date	2009-10-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	225685-x
ISSN	1873-1686 ; 0167-0115
ISSN (online)	1873-1686
ISSN	0167-0115
DOI	10.1016/j.regpep.2009.06.009
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Article: Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents.

Kobelt, Peter / Wisser, Anna-Sophia / Stengel, Andreas / Goebel, Miriam / Bannert, Norbert / Gourcerol, Guillaume / Inhoff, Tobias / Noetzel, Steffen / Wiedenmann, Bertram / Klapp, Burghard F / Taché, Yvette / Mönnikes, Hubert

Peptides

2008 Volume 29, Issue 6, Page(s) 1018–1027

Abstract: Obestatin is produced in the stomach from proghrelin by post-translational cleavage. The initial report claimed anorexigenic effects of obestatin in mice. Contrasting studies indicated no effect of obestatin on food intake (FI). We investigated ... ...

Abstract	Obestatin is produced in the stomach from proghrelin by post-translational cleavage. The initial report claimed anorexigenic effects of obestatin in mice. Contrasting studies indicated no effect of obestatin on food intake (FI). We investigated influences of metabolic state (fed/fasted), environmental factors (dark/light phase) and brain Fos response to intraperitoneal (ip) obestatin in rats, and used the protocol from the original study assessing obestatin effects in mice. FI was determined in male rats injected ip before onset of dark or light phase, with obestatin (1 or 5 micromol/kg), CCK8S (3.5 nmol/kg) or 0.15 M NaCl, after fasting (16 h, n=8/group) or ad libitum (n=10-14/group) food intake. Fos expression in hypothalamic and brainstem nuclei was examined in freely fed rats 90 min after obestatin (5 micromol/kg), CCK8S (1.75 nmol/kg) or 0.15 M NaCl (n=4/group). Additionally, fasted mice were injected ip with obestatin (1 micromol/kg) or urocortin 1 (2 nmol/kg) 15 min before food presentation. No effect on FI was observed after obestatin administration during the light and dark phase under both metabolic conditions while CCK8S reduced FI irrespectively of the conditions. The number of Fos positive neurons was not modified by obestatin while CCK8S increased Fos expression in selective brain nuclei. Obestatin did not influence the refeeding response to a fast in mice, while urocortin was effective. Therefore, peripheral obestatin has no effect on FI under various experimental conditions and did not induce Fos in relevant central neuronal circuitries modulating feeding in rodents.
MeSH term(s)	Animals ; Brain/metabolism ; Brain Stem/metabolism ; Dose-Response Relationship, Drug ; Eating/physiology ; Fasting ; Ghrelin/administration & dosage ; Ghrelin/pharmacology ; Ghrelin/physiology ; Hypothalamus/metabolism ; Immunohistochemistry ; Injections, Intraperitoneal ; Male ; Mice ; Mice, Inbred C57BL ; Photoperiod ; Proto-Oncogene Proteins c-fos/genetics ; Proto-Oncogene Proteins c-fos/metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thinness/physiopathology ; Time Factors
Chemical Substances	Ghrelin ; Proto-Oncogene Proteins c-fos
Language	English
Publishing date	2008-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2008.01.020
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Article: Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats.

Inhoff, Tobias / Mönnikes, Hubert / Noetzel, Steffen / Stengel, Andreas / Goebel, Miriam / Dinh, Q Thai / Riedl, Andrea / Bannert, Norbert / Wisser, Anna-Sophia / Wiedenmann, Bertram / Klapp, Burghard F / Taché, Yvette / Kobelt, Peter

Peptides

2008 Volume 29, Issue 12, Page(s) 2159–2168

Abstract: Studies showed that the metabolic unlike the neuroendocrine effects of ghrelin could be abrogated by co-administered unacylated ghrelin. The aim was to investigate the interaction between ghrelin and desacyl ghrelin administered intraperitoneally on food ...

Abstract	Studies showed that the metabolic unlike the neuroendocrine effects of ghrelin could be abrogated by co-administered unacylated ghrelin. The aim was to investigate the interaction between ghrelin and desacyl ghrelin administered intraperitoneally on food intake and neuronal activity (c-Fos) in the arcuate nucleus in non-fasted rats. Ghrelin (13 microg/kg) significantly increased food intake within the first 30 min post-injection. Desacyl ghrelin at 64 and 127 microg/kg injected simultaneously with ghrelin abolished the stimulatory effect of ghrelin on food intake. Desacyl ghrelin alone at both doses did not alter food intake. Both doses of desacyl ghrelin injected separately in the light phase had no effects on food intake when rats were fasted for 12h. Ghrelin and desacyl ghrelin (64 microg/kg) injected alone increased the number of Fos positive neurons in the arcuate nucleus compared to vehicle. The effect on neuronal activity induced by ghrelin was significantly reduced when injected simultaneously with desacyl ghrelin. Double labeling revealed that nesfatin-1 immunoreactive neurons in the arcuate nucleus are activated by simultaneous injection of ghrelin and desacyl ghrelin. These results suggest that desacyl ghrelin suppresses ghrelin-induced food intake by curbing ghrelin-induced increased neuronal activity in the arcuate nucleus and recruiting nesfatin-1 immunopositive neurons.
MeSH term(s)	Animals ; Arcuate Nucleus of Hypothalamus/drug effects ; Arcuate Nucleus of Hypothalamus/physiology ; Calcium-Binding Proteins ; DNA-Binding Proteins ; Drug Interactions ; Eating/drug effects ; Eating/physiology ; Fasting/physiology ; Ghrelin/administration & dosage ; Ghrelin/pharmacology ; Male ; Nerve Tissue Proteins/metabolism ; Neurons/physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Calcium-Binding Proteins ; DNA-Binding Proteins ; Ghrelin ; Nerve Tissue Proteins ; Proto-Oncogene Proteins c-fos ; ghrelin, des-n-octanoyl ; nucleobindin
Language	English
Publishing date	2008-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2008.09.014
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Article: Peripheral injection of ghrelin induces Fos expression in the dorsomedial hypothalamic nucleus in rats.

Kobelt, Peter / Wisser, Anna-Sophia / Stengel, Andreas / Goebel, Miriam / Inhoff, Tobias / Noetzel, Steffen / Veh, Rüdiger W / Bannert, Norbert / van der Voort, Ivo / Wiedenmann, Bertram / Klapp, Burghard F / Taché, Yvette / Mönnikes, Hubert

Brain research

2008 Volume 1204, Page(s) 77–86

Abstract: Peripheral ghrelin has been shown to act as a gut-brain peptide exerting a potent orexigenic effect on food intake. The dorsomedial nucleus of the hypothalamus (DMH) is innervated by projections from other brain areas being part of the network of nuclei ... ...

Abstract	Peripheral ghrelin has been shown to act as a gut-brain peptide exerting a potent orexigenic effect on food intake. The dorsomedial nucleus of the hypothalamus (DMH) is innervated by projections from other brain areas being part of the network of nuclei controlling energy homeostasis, among others NPY/AgRP-positive fibers arising from the arcuate nucleus (ARC). The aim of the study was to determine if peripherally administered ghrelin affects neuronal activity in the DMH, as assessed by Fos expression. The number of Fos positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), ARC, ventromedial hypothalamic nucleus (VMH), nucleus of the solitary tract (NTS) and in the area postrema (AP) in non-fasted Sprague-Dawley rats in response to intraperitoneally (ip) injected ghrelin (3 nmol/rat) or vehicle (0.15 M NaCl). Peripheral ghrelin induced a significant increase in the number of Fos-ir positive neurons/section compared with vehicle in the ARC (mean+/-SEM: 49+/-2 vs. 23+/-2 neurons/section, p=0.001), PVN (69+/-5 vs. 34+/-3, p=0.001), and DMH (142+/-5 vs. 83+/-5, p<0.001). Fos-ir positive neurons were mainly localized within the ventral part of the DMH. No change in Fos expression was observed in the VMH (53+/-8 vs. 48+/-6, p=0.581), NTS (42+/-2 vs. 40+/-3, p=0.603), and in the AP (7+/-1 vs. 5+/-1, p=0.096). Additional double-labelling with anti-Fos and anti-AgRP revealed that Fos positive neurons in the DMH were encircled by a network of AgRP-ir positive fibers. These data indicate that peripheral ghrelin activates DMH neurons and that NPY-/AgRP-positive fibers may be involved in the response.
MeSH term(s)	Agouti-Related Protein/metabolism ; Animals ; Chromosome Mapping ; Data Interpretation, Statistical ; Dorsomedial Hypothalamic Nucleus/drug effects ; Dorsomedial Hypothalamic Nucleus/metabolism ; Gene Expression/drug effects ; Genes, fos/drug effects ; Ghrelin/pharmacology ; Immunohistochemistry ; Male ; Microscopy, Confocal ; Neuropeptide Y/metabolism ; Rats ; Rats, Sprague-Dawley
Chemical Substances	AGRP protein, rat ; Agouti-Related Protein ; Ghrelin ; Neuropeptide Y
Language	English
Publishing date	2008-02-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2008.01.054
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Article ; Online: First evidence for an association of a functional variant in the microRNA-510 target site of the serotonin receptor-type 3E gene with diarrhea predominant irritable bowel syndrome.

Human molecular genetics

2008 Volume 17, Issue 19, Page(s) 2967–2977

Abstract: Diarrhea predominant irritable bowel syndrome (IBS-D) is a complex disorder related to dysfunctions in the serotonergic system. As cis-regulatory variants can play a role in the etiology of complex conditions, we investigated the untranslated regions ( ... ...

Abstract	Diarrhea predominant irritable bowel syndrome (IBS-D) is a complex disorder related to dysfunctions in the serotonergic system. As cis-regulatory variants can play a role in the etiology of complex conditions, we investigated the untranslated regions (UTRs) of the serotonin receptor type 3 subunit genes HTR3A and HTR3E. Mutation analysis was carried out in a pilot sample of 200 IBS patients and 100 healthy controls from the UK. The novel HTR3E 3'-UTR variant c.76G>A (rs62625044) was associated with female IBS-D (P = 0.033, OR = 8.53). This association was confirmed in a replication study, including 119 IBS-D patients and 195 controls from Germany (P = 0.0046, OR = 4.92). Pooled analysis resulted in a highly significant association of c.76G>A with female IBS-D (P = 0.0002, OR = 5.39). In a reporter assay, c.*76G>A affected binding of miR-510 to the HTR3E 3'-UTR and caused elevated luciferase expression. HTR3E and miR-510 co-localize in enterocytes of the gut epithelium as shown by in situ hybridization and RT-PCR. This is the first example indicating micro RNA-related expression regulation of a serotonin receptor gene with a cis-regulatory variant affecting this regulation and appearing to be associated with female IBS-D.
MeSH term(s)	3' Untranslated Regions/genetics ; Adolescent ; Adult ; Aged ; Case-Control Studies ; Cell Line ; Cohort Studies ; Diarrhea/genetics ; Diarrhea/metabolism ; Female ; Gene Expression ; Germany ; Humans ; Intestinal Mucosa ; Irritable Bowel Syndrome/genetics ; Irritable Bowel Syndrome/metabolism ; Male ; MicroRNAs/genetics ; Middle Aged ; Mutation ; Receptors, Serotonin/genetics ; Receptors, Serotonin/metabolism ; Receptors, Serotonin, 5-HT3 ; Species Specificity ; United Kingdom
Chemical Substances	3' Untranslated Regions ; HTR3A protein, human ; HTR3E protein, human ; MIRN510 microRNA, human ; MicroRNAs ; Receptors, Serotonin ; Receptors, Serotonin, 5-HT3
Language	English
Publishing date	2008-10-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddn195
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