Introdução: A prevalência de doenças crônicas tem crescido em decorrência do aumento da obesidade nos últimos anos. Peptídeos secretados pelo trato gastrointestinal, como o peptídeo semelhante ao glucagon 1 (GLP-1) e o peptídeo YY (PYY), exercem papel fundamental no controle da ingestão alimentar, pois levam informações acerca dos nutrientes ingeridos até o sistema nervoso central, possuindo efeitos anorexígenos e/ou orexígenos. Tanto GLP-1 quanto PYY são produzidos pelas células-L do íleo distal e cólon, sendo liberados após a ingestão alimentar. Além do efeito incretina produzido pelo GLP-1, ambos os peptídeos apresentam implicações no controle do apetite, o qual reflete na redução do peso corpóreo. Objetivos: Demonstrar um aumento na secreção de GLP-1 e PYY após sobrecarga oral de diferentes tipos de lipídios, comparados à controle negativo (água) e positivo (glicose). Métodos: Foi realizado um estudo experimental controlado em ratos Wistar, distribuídos em 4 grupos de acordo com a sobrecarga oral: grupo MUFA (óleo de oliva); grupo SAT (banha suína); grupo GLUC (glicose) e grupo CONT (água), foram avaliadas as concentrações séricas de GLP-1 ativo e PYY3-36 nos tempos: 0, 15, 30, 60 e 120 minutos. As sobrecargas foram isovolumétricas e isocalóricas, com exceção do grupo controle. Resultados: Houve pico de secreção do GLP-1 pós-sobrecarga no grupo MUFA no ponto 120’ vs CONT e GLUC (p≤0,001) e no ponto 30’ quando comparado ao seu baseline. Também observou-se pico de secreção de PYY no grupo MUFA vs CONT no ponto 30’ (p=0,015); no ponto 60’ vs CONT e GLUC (p=0,019) e no ponto 120’ vs CONT e SAT (p=0,02). A carga secretada do PYY foi maior no MUFA quando comparada ao CONT (p=0,04). Verificou-se forte correlação entre os níveis basais e AUC’s do GLP-1 e PYY (r=0,57; (p= 0,02); r=0,39; (p≤0,001)). A proporção GLP-1/PYY apresentou um coeficiente médio de 3,77 (±2,04). O grupo MUFA evidenciou níveis menores de glicose e maiores de insulina no ponto 15’, enquanto SAT mostrou níveis maiores de glicose e menores de insulina neste ponto, porém, sem diferença significativa. Conclusão: A sobrecarga oral de fontes de ácidos graxos monoinsaturados promoveu um pico de secreção do GLP-1 de forma rápida e no que diz respeito ao PYY, o pico foi mais sustentado. Estudos adicionais são necessários, a fim de se avalir o efeito de fontes distintas de lipídeos da dieta sobre a secreção destes peptídeos e seus efeitos na saciedade. / Background: The increased prevalence of chronic diseases has risen due to obesity. Gut peptides, such as glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), play an important role controlling food intake in response to a meal. GLP-1 exerts the known incretin effect stimulating the release of insulin in a glucosedependent manner. Besides its insulinotropic effects, it is well established that GLP-1 slows gastric emptying, and also inhibits inappropriate glucagon release, additionally improves satiety. Both PYY and GLP-1 are produced by L cells of the distal ileum and colon. Objective: Demonstrate an increased secretion of PYY and GLP-1 after oral overload of different types of lipids, compared to negative (water) and positive (glucose) control. Methods: We conducted a controlled experimental study in Wistar rats, divided into 4 groups according to oral overload: MUFA group (olive oil), SAT group (lard:), carbohydrates group (glucose) and CONT group (water), It was evaluated the serum concentration of active GLP-1 and PYY3-36 in the times: 0, 15, 30, 60 and 120 minutes. Overloads were isovolumetric and isocaloric, but the control group. Results: It was verified a higher peak secretion of GLP-1 in MUFA group at 120' after overload vs. CONT and carbohydrates (p ≤ 0.001) and at 30' when compared to its baseline (p=0,01). It was shown a higher secretion peak of GLP-1 after MUFA overload at time 120’ vs CONT e GLUC (p≤0,001) and at time 30’ when compared to its baseline. It was also verified a PYY release peak in MUFA vs CONT at time 30’ (p=0,015); 60’ vs CONT e GLUC (p=0,019) and 120’ vs CONT e SAT (p=0,02). PYY release load presented higher in MUFA group when compared to CONT (p=0,04). A strong correlation was seen between baseline PYY and GLP-1 (r=0,57; p= 0,02) as their AUC’s (r=0,39; p≤0,001). GLP-1/PYY proportion release presented a mean coefficient of 3, 77(±2,04).Conclusion: monounsaturated fatty acids promoted a release peak of GLP-1 in a faster manner and concerning PYY this peak was more sustained. Further studies are necessary to evaluate whether distinct diet fatty acids can ameliorate these gut peptides release and their role on satiety.

Introdução: A prevalência de doenças crônicas tem crescido em decorrência do aumento da obesidade nos últimos anos. Peptídeos secretados pelo trato gastrointestinal, como o peptídeo semelhante ao glucagon 1 (GLP-1) e o peptídeo YY (PYY), exercem papel fundamental no controle da ingestão alimentar, pois levam informações acerca dos nutrientes ingeridos até o sistema nervoso central, possuindo efeitos anorexígenos e/ou orexígenos. Tanto GLP-1 quanto PYY são produzidos pelas células-L do íleo distal e cólon, sendo liberados após a ingestão alimentar. Além do efeito incretina produzido pelo GLP-1, ambos os peptídeos apresentam implicações no controle do apetite, o qual reflete na redução do peso corpóreo. Objetivos: Demonstrar um aumento na secreção de GLP-1 e PYY após sobrecarga oral de diferentes tipos de lipídios, comparados à controle negativo (água) e positivo (glicose). Métodos: Foi realizado um estudo experimental controlado em ratos Wistar, distribuídos em 4 grupos de acordo com a sobrecarga oral: grupo MUFA (óleo de oliva); grupo SAT (banha suína); grupo GLUC (glicose) e grupo CONT (água), foram avaliadas as concentrações séricas de GLP-1 ativo e PYY3-36 nos tempos: 0, 15, 30, 60 e 120 minutos. As sobrecargas foram isovolumétricas e isocalóricas, com exceção do grupo controle. Resultados: Houve pico de secreção do GLP-1 pós-sobrecarga no grupo MUFA no ponto 120’ vs CONT e GLUC (p≤0,001) e no ponto 30’ quando comparado ao seu baseline. Também observou-se pico de secreção de PYY no grupo MUFA vs CONT no ponto 30’ (p=0,015); no ponto 60’ vs CONT e GLUC (p=0,019) e no ponto 120’ vs CONT e SAT (p=0,02). A carga secretada do PYY foi maior no MUFA quando comparada ao CONT (p=0,04). Verificou-se forte correlação entre os níveis basais e AUC’s do GLP-1 e PYY (r=0,57; (p= 0,02); r=0,39; (p≤0,001)). A proporção GLP-1/PYY apresentou um coeficiente médio de 3,77 (±2,04). O grupo MUFA evidenciou níveis menores de glicose e maiores de insulina no ponto 15’, enquanto SAT mostrou níveis maiores de glicose e menores de insulina neste ponto, porém, sem diferença significativa. Conclusão: A sobrecarga oral de fontes de ácidos graxos monoinsaturados promoveu um pico de secreção do GLP-1 de forma rápida e no que diz respeito ao PYY, o pico foi mais sustentado. Estudos adicionais são necessários, a fim de se avalir o efeito de fontes distintas de lipídeos da dieta sobre a secreção destes peptídeos e seus efeitos na saciedade. / Background: The increased prevalence of chronic diseases has risen due to obesity. Gut peptides, such as glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), play an important role controlling food intake in response to a meal. GLP-1 exerts the known incretin effect stimulating the release of insulin in a glucosedependent manner. Besides its insulinotropic effects, it is well established that GLP-1 slows gastric emptying, and also inhibits inappropriate glucagon release, additionally improves satiety. Both PYY and GLP-1 are produced by L cells of the distal ileum and colon. Objective: Demonstrate an increased secretion of PYY and GLP-1 after oral overload of different types of lipids, compared to negative (water) and positive (glucose) control. Methods: We conducted a controlled experimental study in Wistar rats, divided into 4 groups according to oral overload: MUFA group (olive oil), SAT group (lard:), carbohydrates group (glucose) and CONT group (water), It was evaluated the serum concentration of active GLP-1 and PYY3-36 in the times: 0, 15, 30, 60 and 120 minutes. Overloads were isovolumetric and isocaloric, but the control group. Results: It was verified a higher peak secretion of GLP-1 in MUFA group at 120' after overload vs. CONT and carbohydrates (p ≤ 0.001) and at 30' when compared to its baseline (p=0,01). It was shown a higher secretion peak of GLP-1 after MUFA overload at time 120’ vs CONT e GLUC (p≤0,001) and at time 30’ when compared to its baseline. It was also verified a PYY release peak in MUFA vs CONT at time 30’ (p=0,015); 60’ vs CONT e GLUC (p=0,019) and 120’ vs CONT e SAT (p=0,02). PYY release load presented higher in MUFA group when compared to CONT (p=0,04). A strong correlation was seen between baseline PYY and GLP-1 (r=0,57; p= 0,02) as their AUC’s (r=0,39; p≤0,001). GLP-1/PYY proportion release presented a mean coefficient of 3, 77(±2,04).Conclusion: monounsaturated fatty acids promoted a release peak of GLP-1 in a faster manner and concerning PYY this peak was more sustained. Further studies are necessary to evaluate whether distinct diet fatty acids can ameliorate these gut peptides release and their role on satiety.

Abstract Parasites are an inseparable part of the life of wild birds. They may cause morbidity, mortality or reduction in fecundity. Parasite distribution in hosts is typically not uniform and many host factors (e.g. age) may affect the pattern of distribution. Under certain conditions, parasites even have the potential to regulate the host population. The grouse species of Finnish forests — the capercaillie Tetrao urogallus , the black grouse Lyrurus tetrix and the hazel grouse Tetrastes bonasia — harbour several species of intestinal helminth parasites. The populations have fluctuated in cyclic manner but the mechanisms behind the cycles are largely unknown. I studied the interactions of forest grouse and their intestinal helminth parasites by using intestinal samples collected by hunters in five game management districts during eight years (1995–2002). The most common parasite species in the samples was the nematode Ascaridia compar. Also, three species of cestodes (Skrjabinia cesticillus, Paroniella urogalli and Hymenolepis sp.) were found. Large size, male gender and age over 1 year were connected with an increased probability and intensity of A. compar infection. Juvenile grouse were commonly infected with cestodes while in adults infections were quite rare. The influence of inbreeding on the susceptibility to parasite infections was studied in the capercaillie by analysing microsatellite heterozygosity. The less heterozygous birds were more likely to be infected with A. compar and were more intensely infected suggesting negative influence of inbreeding on parasite resistance. An indirect negative effect of parasites was found by comparing bags hunted with a trained dog or without a dog. Grouse infected by cestodes were significantly more common in the dog-assisted bag. Thus, cestode infection seemed to make grouse more vulnerable to canine predation. The interaction between grouse population dynamics and parasites was studied by analyzing the grouse densities obtained from annual wildlife counts and parasite indices. A. compar was most common and most abundant in the years of grouse population decline. The grouse population growth rate was negatively correlated with the annual mean abundance of A. compar. Relative survival but not breeding success decreased as the abundance of A. compar increased. The findings suggest that A. compar influences the dynamics of Finnish grouse even though regular cyclic dynamics are no longer evident. / Tiivistelmä Loiset kuuluvat erottamattomana osana luonnonvaraisten lintujen elämään. Ne voivat aiheuttaa sairautta, kuolleisuutta tai hedelmällisyyden alentumista. Tyypillisesti loiset ovat levinneet isäntäpopulaatioon epätasaisesti ja monet isännän ominaisuudet (esim. ikä) vaikuttavat levinneisyyteen. Tietyissä oloissa loiset voivat jopa säädellä isäntäpopulaatiotaan. Suomalaiset metsäkanalinnut — metso Tetrao urogallus, teeri Lyrurus tetrix ja pyy Tetrastes bonasia — ovat useiden suolistoloismatolajien isäntiä. Metsäkanapopulaatiot ovat vaihdelleet syklisesti, mutta syklejä aiheuttavat mekanismit ovat yhä tuntemattomia. Tutkin metsäkanalintujen ja niiden suolistoloisten välisiä vuorovaikutuksia käyttäen metsästäjien vuosina 1995–2002 viidestä eri riistanhoitopiiristä keräämiä suolistonäytteitä. Yleisin loislaji näytteissä oli kanalintusuolinkainen, Ascaridia compar. Myös kolme heisimatolajia (Skrjabinia cesticillus, Paroniella urogalli ja Hymenolepis sp.) todettiin. Suuri koko, koirassukupuoli ja yli yhden vuoden ikä olivat yhteydessä suurempaan kanalintusuolinkaistartunnan todennäköisyyteen ja voimakkuuteen. Nuorilla (alle 1 v.) linnuilla heisimadot olivat yleisiä, kun taas aikuisilla tartunnat olivat varsin harvinaisia. Sisäsiittoisuuden vaikutusta loistartuntaherkkyyteen tutkittiin metsolla mikrosatelliittiheterotsygotian perusteella. Vähemmän heterotsygoottiset metsot olivat todennäköisemmin ja voimakkaammin suolinkaisten infektoimia, mikä viittaa sisäsiittoisuuden negatiiviseen vaikutukseen loisten vastustuskykyyn. Loisten epäsuora haitallinen vaikutus havaittiin, kun verrattiin koiran kanssa ja ilman koiraa metsästettyä lintusaalista. Heisimadot olivat selvästi yleisempiä linnuilla, jotka oli metsästetty koiran kanssa kuin ilman koiraa metsästetyillä. Heisimatotartunta näytti siis altistavan metsäkanoja koiraeläinten saalistukselle. Metsäkanalintu- ja loispopulaatioiden välistä vuorovaikutusta tutkittiin analysoimalla vuosittaisia metsäkanatiheyksiä ja loisten runsautta. Kanalintusuolinkainen oli yleisimmillään ja runsaimmillaan metsäkanatiheyden laskuvuosina. Metsäkanapopulaation vuosittainen kasvuvauhti korreloi negatiivisesti kanalintusuolinkaisen vuosittaisen runsauden kanssa. Suhteellinen elossasäilyvyys laski kanalintusuolinkaisen runsauden lisääntyessä, mutta lisääntymistuloksen suhteen ei ollut samaa ilmiötä. Löydökset viittaavat siihen, että kanalintusuolinkaisella on vaikutusta suomalaisten metsäkanalintukantojen vaihteluihin, vaikka syklisiä kannanvaihteluja ei enää havaitakaan.

Bypass or resection of the stomach and oesophagus, has long been recognised to result in profound changes in the handling of ingested nutrients. This results in significant morbidity after radical surgery for oesophago-gastric cancer, in particular post-prandial hypoglycaemia, altered appetite, early satiety and noxious post-prandial symptoms. By profiling and challenging the gut hormone axis in healthy volunteers and patients who had undergone total or subtotal gastrectomy, or oesophagectomy, this thesis explores the possible causative mechanisms for the challenges faced by this patient population. In the surgical groups, an oral glucose tolerance test (OGTT) resulted in enhanced secretion of satiety and incretin gut hormones (GLP-1, GIP, PYY) and insulin, followed by hypoglycaemia in a cohort of patients. Continuous glucose monitoring of gastrectomy participants over two weeks of normal lifestyle identified an increased incidence of day and night time hypoglycaemia. RNAseq and mass spectrometry based peptidomics of human and murine enteroendocrine cells in the pre- and post-operative populations revealed no significant change in the underlying cellular pathways for nutrient sensing and gut hormone secretion, indicating that the altered hormone secretion is primarily driven by accelerated nutrient transit, rather than adaptive changes in the gut. Finally, specific blockade of the GLP-1 receptor in post-gastrectomy patients using Exendin 9-39 normalised insulin secretion and prevented reactive hypoglycaemia after an OGTT. In conclusion, profound changes in gut hormone secretion as a result of enhanced nutrient transit after foregut surgery likely underlie the early and late post-prandial symptoms seen in this group, and therapies specifically targeting the gut hormone axis, and GLP-1 in particular, could be the first targeted treatments for post-gastrectomy syndromes.