Thesis (M.S.)--Ohio University, June, 2005. / Title from PDF t.p. Includes bibliographical references (p. 88-96)

nÃo hà / A perda de peso à uma queixa comum dos pacientes com doenÃa de Crohn, estando a desnutriÃÃo presente em 30-80% dos portadores dos casos. Foi demonstrado que pacientes com doenÃa de Crohn em inatividade apresentam sintomas dispÃpticos relacionados com alteraÃÃo no esvaziamento gÃstrico. No entanto, a correlaÃÃo da atividade da doenÃa com os parÃmetros antropomÃtricos, nutricionais e de saciedade ainda à objeto de investigaÃÃo. Portanto, o objetivo do nosso estudo foi correlacionar a atividade da doenÃa com o estado nutricional, sintomas dispÃpticos, esvaziamento gÃstrico, saciedade e nÃveis de grelina em pacientes com doenÃa de Crohn. Trata-se de um estudo transversal, analÃtico e quantitativo realizado em vinte pacientes com doenÃa de Crohn, classificados segundo um Ãndice de Atividade de DoenÃa de Crohn (Crohnâs Disease Activity Index â CDAI). Os pacientes foram submetidos a uma avaliaÃÃo nutricional, que se fundamentou na utilizaÃÃo de mÃtodos duplamente indiretos (Ãndice de massa corporal, dobra cutÃnea tricipital e circunferÃncia do braÃo). AlÃm disso, nos pacientes foi avaliado o consumo alimentar atravÃs de um recordatÃrio alimentar. Estes foram tambÃm submetidos a uma anÃlise do tempo de esvaziamento gÃstrico por teste respiratÃrio usando o 13C - Ãcido octanÃico ligado a uma refeiÃÃo sÃlida - e responderam a um questionÃrio validado (QuestionÃrio Porto Alegre de Sintomas DispÃpticos) para avaliar os sintomas dispÃpticos. Outro teste realizado foi o teste de saciedade(drinking test), no qual o paciente ingeriu 15 ml de uma bebida lÃquida padrÃo(Nutridrink), e era lhe perguntado o nÃvel de saciedade atravÃs de uma escala analÃgica. Durante o teste respiratÃrio, foram realizadas coletas de amostras de sangue para dosagem de grelina: basal( jejum) e pÃs-prandial. Os dados foram analisados estatisticamente pelos testes: t de Student, exato de Fisher, Mann-Whitney e correlaÃÃo de Spearman. Observou-se que os parÃmetros CDAI e IMC (p=0,0185) e CB (p=0,023) foram inversamente proporcionais, porÃm nÃo houve diferenÃa estatÃstica entre as correlaÃÃes do CDAI com prega cutÃnea tricipital( p=0,0543). Os pacientes nÃo apresentaram correlaÃÃo da atividade da doenÃa com o esvaziamento gÃstrico ( t Â- p=0,2533; t lag-p=0,3079). Entretanto, houve correlaÃÃo significativa do CDAI com todos os sintomas dispÃpticos (p=0,005). NÃo se verificou correlaÃÃo da atividade da doenÃa e o volume de lÃquido suportado. Entretanto, a atividade da doenÃa influenciou os nÃveis de grelina no pÃs-prandial (p=0,04). CONCLUSÃO: A atividade da doenÃa correlaciona-se com o estado nutricional, a presenÃa de sintomas dispÃpticos e nÃveis de grelina de pacientes portadores de doenÃa de Crohn. Entretanto nÃo existe correlaÃÃo com alteraÃÃes no esvaziamento gÃstrico e saciedade sugerindo que outros mecanismos possam estar envolvidos.

Ghrelin is a gut peptide produced by mainly stomach that induces appetite stimulatory actions. Obestatin is peptide derived from preproghrelin and was initially described to antagonize stimulatory effect of ghrelin on food intake. This work was undertaken to investigate the influence of postprandial status on plasma ghrelin and obestatin concentrations in patients with bulimia nervosa and healthy women. After overnight fasting, plasma ghrelin and obestatin were measured before and after consumption of soluble fiber alone or with glucose. I observed greater decrease of plasma ghrelin and obestatin after consumption of soluble fiber with glucose. I conclude that postprandial plasma ghrelin and obestatin levels are influenced by caloric content of the meal and depend on eating behavior.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19887号 / 医博第4136号 / 新制||医||1016(附属図書館) / 32964 / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 横出 正之, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

This study was to determine (1) if genetic selection for high (HWS) or low (LWS) body weight in chickens has altered the hypothalamic AMP-activated protein kinase (AMPK) system and (2) if this alteration contributes to the dissimilar feeding response to various appetite modulators between HWS and LWS lines. Compared to HWS, LWS chickens had higher levels of AMPK α and acetyl-CoA carboxylase (ACC) phosphorylation, which was caused by upregulation of the upstream factor calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK β). There was greater mRNA expression of carnitine palmitoyltransferase I (CPT1), leptin receptor (LEPR) and neuropeptide Y (NPY) and less mRNA expression of ACC α, fatty acid synthase (FAS), fat mass and obesity associated gene (FTO), pro-opiomelanocortin (POMC) and orexin in LWS than HWS chickens. At 5 days of age, intracerebroventricular (ICV) injection of AICAR, 5-amino- 4-imidazolecarboxamide riboside, caused a quadratic dose-dependent decrease in food intake in LWS but not HWS chicks. Compound C, (6-(4-(2-piperidin-1-yl-ethoxy)-phenyl))-3-pyridin-4-yl-pyrazolo(1,5-a)-pyrimidine, caused a quadratic dose-dependent increase in food intake in HWS but not LWS chicks. The anorexigenic effect of AICAR in LWS chicks and orexigenic effect of Compound C in HWS chicks resulted from either activation or inhibition of other kinase pathways separate from AMPK. There is a lower threshold for the anorexigenic effect of ghrelin in LWS than HWS chicks, which was associated with differential hypothalamic AMPK signaling. ICV injection of ghrelin inhibited corticotrophin-releasing hormone (CRH), 20-hydroxysteroid dehydrogenase (20HSD), glucocorticoid receptor (GR), CPT1 and FTO expression in LWS but not HWS chicks. Additionally, the hypothalamic mRNA level of ghrelin was significantly higher in LWS than HWS chicks, which may also contribute to the differential threshold response to ghrelin in these two lines. Obestatin caused a linear dose-dependent increase in food intake in HWS but not LWS chicks. The orexigenic effect of obestatin in HWS chicks was not associated with altered AMPK. Obestatin inhibited LEPR and FTO expression in HWS but not LWS chicks. Thus, selection for body weight may alter the hypothalamic response to ghrelin by the AMPK pathway, CRH pathway, CPT1 and FTO, and to obestatin by LEPR and FTO. / Ph. D.

<p>Enterochromaffin-like (ECL) and ghrelin cells, in the human gastric mucosa and in gastric endocrine tumours (GETs), were subclassified with respect to immunohistochemical reaction <i>vs.</i> vesicular monoamine transporter 2 (VMAT-2), ghrelin/obestatin, and histidine decarboxylase (HDC). The immunohistochemical expression of ghrelin/obestatin and HDC in GETs was related/correlated to plasma ghrelin/obestatin and urinary methyl imidazole acetic acid (U-MeImAA) excretion respectively, with the intention of identifying markers for these tumour types. </p><p>ECL cells in the gastric mucosa appear either with VMAT-2 only, or with HDC immunoreactivity only, or they can express both proteins; but in GETs the transporter protein and the enzyme were almost always co-expressed in the same cells. Furthermore, ghrelin and obestatin were co-localized in the same cells in the gastric mucosa and in the tumours. In the gastric mucosa, occasional ghrelin/obestatin cells expressed VMAT-2, but in GETs these proteins were always co-localized. Ghrelin expressing cells were non-immunoreactive to HDC. Plasma ghrelin/obestatin concentrations remained low in patients with GETs, irrespective of the relative incidence of these cells in the mucosa and in tumours. The plasma values were not related/correlated to various clinico-pathological parameters. A malignant ghrelinoma was however an exception. The tumour released high total and active ghrelin concentrations into the blood circulation. The patient suffered from diarrhoea, hypothyroidism and diabetes mellitus, but it is not clear if these conditions were due to hyperghrelinaemia. The excretion U-MeImAA was increased in a few patients with GETs, but this increase was not always related to clinical symptoms.</p><p>In conclusion, ECL cells are an heterogeneous group according to VMAT-2 and HDC immunoreactivity. Ghrelin and obestatin are expressed in the same cells in the gastric mucosa, and a few of these cells display VMAT-2 immunoreactivity. Ghrelinoma is a new gastric tumour entity.</p>

BACKGROUND & AIMS: Psychological stress in early childhood has been implicated in the pathophysiology of functional dyspepsia but the mechanism is unclear. This study investigates the effect of early psychological stress on the regulation of satiety function in adulthood using an animal model of neonatal maternal separation stress (NMSS). / CONCLUSIONS: Psychological stress in early life leads to aberrant ghrelin profile and dysregulation of feeding behavior in response to acute psychological or physiological stress in adulthood. / METHODS: Sprague-Dawley (SD) rats underwent 3-hour daily maternal separation (MS) from postnatal day 2 to 22 and were weaned. The rats with no MS served as non-handling controls. Three experiments were conducted on these rats on day 60: (1) Water avoidance stress (WAS); (2): Feeding after overnight fasting and (3) Feeding after overnight fasting and WAS. Serial blood samples were collected for acylated ghrelin (AG) assay. In experiments (1) and (2), tissues from the stomach and hypothalamus were harvested additionally for evaluation of ghrelin expression. In experiments (2) and (3), calorie intake was also monitored at regular time intervals. / RESULTS: Experiment (1): MS rats had significantly higher mRNA ghrelin in hypothalamus (1.012 +/- 0.098 vs 0.618 +/- 0.071, P = 0.009) and plasma AG level (141.6 +/- 28.92 pg/mL vs 97.69 +/- 38.21 pg/mL, P = 0.014) in baseline non-stressed conditions. After WAS, MS rats had further increase in plasma AG level and gastric ghrelin expression. Experiment (2): After overnight fasting, the initial calorie intake was significantly higher in MS rats (at 3 mins: 1.303 +/- 0.293 kcal vs 0.319 +/- 0.159 kcal, P= .011; at 8 mins: 2.578 +/- 0.207 kcal vs 1.299 +/- 0.416 kcal, p = 0.019) but it dropped abruptly afterward and no difference in overall calorie intake over 28 minutes was found. The postprandial plasma AG level and gastric mRNA ghrelin were significantly lower in MS rats (95.92 +/- 12.71 pg/mL vs 154.01 +/- 14.53 pg/mL, p = 0.010). Experiment (3): After both fasting and WAS, the MS rats had significantly higher calorie intake in the first hour (17.24 +/- 1.10 kcal vs 11.95 +/- 1.20 kcal, P= 0.006) but it dropped substantially afterward with significantly lower cumulative calorie intake at 3 hours (at 3 hr: 19.44 +/- 1.50 kcal vs 26.49 +/- 2.25 kcal, P = 0.023). The calorie intake in MS rats remained significantly lower than that of controls up to 48 hours (168.1 +/- 4.76 kcal vs 220.8 +/- 8.27 kcal, P&lt; 0.001). / Cheung, Kwan Yui Cynthia. / Adviser: Justin C.Y. Wu. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 138-154). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Ghrelin is a unique hunger-inducing stomach-borne hormone. It activates orexigenic circuits in the central nervous system (CNS) when acylated with a fatty acid residue by the Ghrelin O-acyltransferase (GOAT). Soon after the discovery of ghrelin a theoretical model emerged which suggests that the gastric peptide ghrelin is the first “meal initiation molecule”. Ghrelin is also termed “hunger hormone” with a potentially important role as an endogenous regulator of energy balance. However, genetic deletion of ghrelin or its receptor, the growth hormone secretagogue receptor (GHSR), has only limited effects on appetite and obesity. Here we introduce novel mouse models of altered ghrelin, GHSR and GOAT function to reevaluate the role of the ghrelin system in regulating energy homeostasis. Simultaneous loss of ghrelin and GHSR function leads to decreased body weight and body fat, likely caused by increased energy expenditure and locomotor activity. Similarly, GOAT deficient mice are lighter and leaner than the wild-type controls. Mice overexpressing ghrelin and GOAT have increased body weight and fat mass along with decreased energy expenditure. Wild-type mouse studies show that fasting induces downregulation of the GOAT gene Mboat4 and decreases acyl ghrelin concentration in blood. We therefore hypothesized that GOAT rather depends on dietary than endogenous derived lipids for ghrelin acylation. Feeding studies show that GOAT uses the unnatural fatty acid heptanoate (C7) to acylate ghrelin, which clearly supports our theory. Further, acylation of overproduced ghrelin in our transgenic mouse model requires dietary supplementation of medium-chain-triglycerides, the preferred GOAT substrate. Our genetic models suggest that the ghrelin system plays an important physiological role in the control of energy metabolism. Thus, GOAT offers a novel peripheral drug target for the treatment of metabolic diseases. Moreover, our results suggest that ghrelin signaling may not be a result of absent nutrient intake, but indicate the availability of dietary lipids. We therefore propose that the ghrelin system functions as a novel lipid sensor, linking specific dietary lipids with the central-nervous control of energy metabolism. / Ghrelin ist ein einzigartiges im Magen produziertes Hormon, da es von dem Enzym Ghrelin O-acyltransferase (GOAT) mit einer mittelkettigen Fettsäure acyliert werden muss, um biologische Aktivität zu erlangen. Kurz nach seiner Entdeckung entstand die Hypothese, dass Ghrelin das „Hungerhormon“ sei und eine wichtige Rolle in der Regulation des Energiehaushalts spiele. Die genetische Manipulation von Ghrelin und seinem Rezeptor, dem GHSR, hat jedoch nur geringe Auswirkung auf Appetit und Körpergewicht. In der hier vorliegenden Studie stellen wir neuartige Mausmodelle mit abgewandelter Ghrelin-, GHSR- und GOATfunktion vor, um den Einfluss des Ghrelinsystems auf die Regulation der Energiehomöostase zu reevaluieren. Weiterhin wird die endogene Regulation von GOAT erstmalig beschrieben. Double-knockout Mäuse, die gleichzeitig defizitär für Ghrelin und GHSR sind, haben ein geringeres Körpergewicht, weniger Fettmasse und einen niedrigeren Energieverbrauch als Kontrolltiere. Knockout Mäuse für das GOAT Gen Mboat4 sind leichter und schlanker als Kontrolltiere. Dementsprechend haben transgene Mäuse, die Ghrelin und GOAT überproduzieren, eine erhöhte Fettmasse und einen verminderten Energieverbrauch. Weiterhin können wir zeigen, dass GOAT, anders als auf Grund der allgemein bekannten Ghrelinfunktion angenommen, nicht durch Hungern aktiviert wird. Bei Mäusen, die gefastet haben, ist die Genexpression von Mboat4 deutlich herunterreguliert, woraus ein geringer Blutspiegel von Acyl-Ghrelin resultiert. Daraus haben wir geschlossen, dass GOAT eventuell Nahrungsfette und nicht die durch Hungern freigesetzten endogen Fettsäuren zur Ghrelinacylierung benutzt. Fütterungsversuche bestätigen diese Hypothese, da GOAT die unnatürliche Fettsäure Heptan Säure (C7), die der Tiernahrung beigefügt wurde, zur Ghrelinacylierung verwendet. Ein weiteres Indiz für die Notwendigkeit von Nahrungsfetten für die Ghrelinacylierung ist, dass die transgenen Ghrelin/GOAT Mäuse nur massiv Acyl-Ghrelin produzieren, wenn sie mit einer Diät gefüttert werden, die mit mittelkettigen Fettsäuren angereichert ist. Zusammenfassend zeigt die Studie, dass das Ghrelinsystem maßgeblich an der Regulation der Energiehomöostase beteiligt ist und dass die Ghrelinaktivierung direkt von Nahrungsfetten beeinflusst wird. Daraus könnte geschlossen werden, dass Ghrelin wohlmöglich nicht das Hungerhormon ist, wie bisher generell angenommen wurde. Ghrelin könnte vielmehr ein potentieller “Fettsensor” sein, der dem Gehirn die Verfügbarkeit von fettreicher Nahrung signalisiert und somit den Metabolismus zur optimalen Verwertung und Speicherung der aufgenommenen Energie beeinflusst.

Enterochromaffin-like (ECL) and ghrelin cells, in the human gastric mucosa and in gastric endocrine tumours (GETs), were subclassified with respect to immunohistochemical reaction vs. vesicular monoamine transporter 2 (VMAT-2), ghrelin/obestatin, and histidine decarboxylase (HDC). The immunohistochemical expression of ghrelin/obestatin and HDC in GETs was related/correlated to plasma ghrelin/obestatin and urinary methyl imidazole acetic acid (U-MeImAA) excretion respectively, with the intention of identifying markers for these tumour types. ECL cells in the gastric mucosa appear either with VMAT-2 only, or with HDC immunoreactivity only, or they can express both proteins; but in GETs the transporter protein and the enzyme were almost always co-expressed in the same cells. Furthermore, ghrelin and obestatin were co-localized in the same cells in the gastric mucosa and in the tumours. In the gastric mucosa, occasional ghrelin/obestatin cells expressed VMAT-2, but in GETs these proteins were always co-localized. Ghrelin expressing cells were non-immunoreactive to HDC. Plasma ghrelin/obestatin concentrations remained low in patients with GETs, irrespective of the relative incidence of these cells in the mucosa and in tumours. The plasma values were not related/correlated to various clinico-pathological parameters. A malignant ghrelinoma was however an exception. The tumour released high total and active ghrelin concentrations into the blood circulation. The patient suffered from diarrhoea, hypothyroidism and diabetes mellitus, but it is not clear if these conditions were due to hyperghrelinaemia. The excretion U-MeImAA was increased in a few patients with GETs, but this increase was not always related to clinical symptoms. In conclusion, ECL cells are an heterogeneous group according to VMAT-2 and HDC immunoreactivity. Ghrelin and obestatin are expressed in the same cells in the gastric mucosa, and a few of these cells display VMAT-2 immunoreactivity. Ghrelinoma is a new gastric tumour entity.