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< 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.

Orientador: Bruno Geloneze Neto / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T12:17:34Z (GMT). No. of bitstreams: 1 Cardozo_DanielaSchiavo_D.pdf: 1355414 bytes, checksum: 3c91c18e1699608cf367e306cda835af (MD5) Previous issue date: 2012 / Resumo: Devido ao aumento considerável de trabalhadores noturnos é importante o estudo dos efeitos deste tipo de trabalho na saúde do trabalhador. Estudos atuais demonstram que trabalhos em turno e noturno favorecem transtornos digestivos relacionados a diferenças no hábito alimentar, tanto no valor calórico total, como no horário e número de refeições. Além disso, há aumento dos fatores de risco cardiovasculares, tais como: altos níveis de triglicérides e colesterol séricos, obesidade abdominal, resistência à insulina e outros marcadores da síndrome metabólica. Estes fenômenos estão relacionados a um ganho e redistribuição do peso corporal, em parte atribuível a diferenças no padrão de fome e saciedade. Trabalhadores do turno noturno podem apresentar perturbação no ritmo biológico endógeno em função do conflito temporal entre o relógio biológico endógeno e a estrutura de funcionamento das atividades sociais. Esta dessincronização pode produzir transtornos intensos e persistentes na fisiologia do sono. Foram selecionados 12 trabalhadoras de turno noturno e 12 do diurno do HC-UNICAMP, com IMC entre 25 e 29.9 (sobrepeso). O objetivo deste trabalho foi comparar uma população trabalhadora de turno noturno com uma população trabalhadora diurna, em relação a componentes bioquímicos e antropométricos da síndrome metabólica. Além disso, a caracterização das respostas de hormônios reguladores da fome e saciedade foi acessada a partir de um teste de refeição padrão, com dosagens de grelina, (hormônio orexigênico), oxintomodulina, xenina, glucagon-like peptide 1 (GLP-1) e PYY3-36 (hormônios anorexigênicos). A resistência à insulina foi avaliada por índices que relacionam a produção de insulina com a curva glicêmica durante o teste de refeição (Metabolic Clearance Rate, ou índice de Stumvoll). Estes mesmos voluntários foram avaliados quanto à qualidade de sono, ao cronótipo e ao estado inflamatório sub-clínico (avaliado pelos níveis circulantes de interleucina 6, TNF-?, adiponectina e proteína C-reativa). Na avaliação quanto ao cronótipo, a maior proporção de indivíduos indiferentes foram encontrados no grupo do turno noturno. A qualidade de sono avaliada pelo score de Pittsburgh não demonstrou diferença significante entre os grupos estudados. Os trabalhadores de turno noturno demonstraram valores maiores para disfunção diurna, demonstrando sonolência excessiva diurna. O principal achado foi a caracterização de uma resposta de produção do hormônio orexigênico - grelina - aumentada no período pós-prandial das voluntárias de trabalho noturno e uma resposta reduzida de xenina (um hormônio anorexígeno e de fonte estomacal). Assim este fato pode ser responsável pela mudança do comportamento alimentar e consequente ganho de peso destas trabalhadoras de turno noturno. / Abstract: Due to the considerable increase of night shift workers it is important the study of its effects on worker health. Recent studies reveal that work in shifts and night shift work propitiate digestive disorders related to differences in dietary habits, in the total caloric content, as well as in the timing and number of meals. Moreover, it is noticed an increase in cardiovascular risk factors such as high levels of triglycerides and cholesterol, and abdominal obesity, insulin resistance and markers of metabolic syndrome. These phenomena are related to gain and redistribution of body weight, in part attributable to changes in the pattern of hunger and satiety. Night shift workers may have endogenous biological rhythm disturbance as a result of the temporal conflict between the endogenous biological clock and the functioning structure of social activities. This asynchronization may produce intense and persistent disorders in sleep physiology. We selected 12 night shift workers and 12 day workers of the HC-UNICAMP, with BMI between 25 and 29.9 (overweight). The objective of this study was to compare a population of night shift workers with a daytime working population in relation to anthropometric and biochemical components of the metabolic syndrome. Besides that, the characterization of the responses of hormones regulating hunger and satiety was accessed by means of a standard meal test , with dosages of ghrelin, oxyntomodulin, xenin, glucagon-like peptide 1 (GLP-1) and PYY3-36. Insulin resistance was evaluated by indexes relating the production of insulin during the glycemic test meal (Stumvol index). These same volunteers were evaluated for the quality of sleep, the chronotype and sub-clinical inflammatory state (assessed by circulating levels of interleukin-6, TNF-?, adiponectin and protein C-reactive). In the assessment for the chronotype, the highest proportion of indifferent individuals were found in the group of night shift. The quality of sleep assessed by pittsburgh score showed no significant difference between groups. The night shift workers showed higher values for daytime dysfunction, demonstrating excessive daytime sleepiness. The main finding was the characterization of a increased response in production of hormone - ghrelin - in the postprandial period of night shift workers and reduced response of xenina (an anorectic hormone source and stomach). As a conclusion, this fact may be responsible for the weight gain observed for those night shift workers. / Doutorado / Clinica Medica / Doutora em Clínica Médica