Indiana University-Purdue University Indianapolis (IUPUI) / Obesity is a growing pandemic that claims close to three hundred thousand lives per year in the United States alone. Despite strong interest and investment in potential treatments, obesity remains a complex and challenging disorder. In the study of obesity, mouse models have been excellent tools that help in understanding the function of different genes that contribute to this disease of energy homeostasis. However, it was surprising when disfunction in primary cilia was found to be linked to syndromic obesity. To understand the role of primary cilia in obesity, a growing subset of GPCRs have been identified to selectively localize to the organelle. Several of which have known roles in energy homeostasis. In some examples, ciliary GPCRs appear to dynamically localize to the organelle; such is the case of GPR161 and smoothened in the hedgehog signaling pathway. Thus, we were interested to see if other GPCRs dynamically localize to the primary cilia as part of their regulation of energy homeostasis. For example, the GPCR MCHR1 selectively localizes to the cilia and is involved in energy homeostasis. Although much is known about the expression of the receptor in the brain, how its ciliary subcellular localization impacts its roles in energy homeostasis is unknown. Observing neuronal cilia in vivo remains a difficult task as some of the available tools such as tagged alleles rely on overexpression of ciliary protein which may impact function. Additionally, most of the work is done in vitro, leaving much to be discovered about neuronal cilia in vivo. In this thesis, we show that using a newly constructed reporter allele mCherryMCHR1, we can see ciliary expression of MCHR1 in the brain of developing and adult mice; more specifically in the ARC and PVN. Subsequently, using a novel Artificial intelligence analysis approach, we measured the length and composition of MCHR1 positive cilia under physiological conditions associated with MCHR1 function. Although in this work we are reporting no changes in dynamic localization of MCHR1 in the hypothalamus specifically, we are not excluding the potential for changes in other regions of the brain or under other conditions; and we are suggesting that pharmacological approaches may help highlight potential ciliary GPCR dynamic localization.

Estudou-se o efeito da alimentação, do jejum e da realimentação sobre o perfil metabólico e ruminal de bovinos em crescimento. Para tal, empregaram-se 12 garrotes mestiços, com cerca de 300 kg, obtendo-se amostras de sangue e fluido ruminal no decorrer dos seguintes períodos: 11 horas de alimentação normal (período pós-prandial), 48 horas consecutivas de jejum alimentar, seguida de 48 horas de realimentação. Comparado com o período pós-prandial, o jejum provocou as seguintes modificações: moderada hipoglicemia; acompanhada por marcante lipólise, detectada pelo aumento nos teores plasmáticos de ácidos graxos livres; ausência de lipidose hepática, visto que não ocorreram alterações na atividade da aspartato aminotransferase e nos teores de colesterol sérico; discreta cetogênese, confirmada pela pequena elevação de β-hidroxibutirato; e certo grau de proteólise, verificado pelo aumento dos teores de uréia sérica e da excreção urinária de uréia. Nesse mesmo período ocorreu uma ligeira hipovolemia, caracterizada pelo aumento no déficit de volume intravascular. Este quadro metabólico verificado durante o jejum foi completamente revertido durante a realimentação, com exceção da proteólise que foi temporariamente maior. O jejum provocou notável modificação no perfil ruminal: intensa elevação no pH do fluido; diminuição marcante na flora e fauna que foi detectada, respectivamente, pela menor quantidade de matéria seca bacteriana e expressiva redução no número de protozoários; notória elevação no tempo de redução do azul de metileno; queda no índice de excreção urinária de alantoína, contudo sem alteração no índice de excreção urinária de ácido úrico. A realimentação promoveu completa e rápida recuperação das variáveis do perfil ruminal, com exceção do número de protozoários, que embora tenha se elevado, não atingiu os valores basais. A prova de redução de azul de metileno apresentou alta correlação positiva (r = 0,89) com a quantidade de matéria seca bacteriana. Devido à facilidade, rapidez e praticidade de ser conduzida e a alta sensibilidade indica-se a prova de redução do azul de metileno como teste de eleição na análise do perfil ruminal. / The effect of feeding, fasting and refeeding on metabolic and ruminal profile of steers was studied. Thus, blood and ruminal samples were drawn of twelve 300 kg crossbred steers throughout three different periods: 11 hour during normal feeding, 48 hour of fasting followed by the same time of refeeding. The fasting caused a moderate hypoglycemia, followed by marked lipolysis, detected by the high plasma free fatty acid concentration, but there was no evidence of hepatic lipidosis, since there were no changes in the activity of aspartate aminotransferase and serum cholesterol levels; a discrete ketogenesis occurred as there was a slight increase in the β-hidroxibutirate concentration; proteolysis were detected by the increase of serum and urinary excretion of urea. During the fasting the animals developed a slight hypovolemia detected by the increase of the plasma volume deficit. These metabolic changes were completely reversed during the refeeding, but the proteolysis had a temporary increase. The fasting gave rise to deeply changes in the ruminal profile, such as: increase in the rumen pH, reduction the number of rumen protozoa and bacteria, as seen by the low bacteria dry matter; increase in the methylene blue reduction time and lowering of the urinary excretion of allantoin, but no changes were seen in the uric acid urinary level. The refeeding made the rumen status return to normal, but the protozoa number that despite a slight increase was very far away from the basal standard. There was a high (r = 0.89) positive correlation between the methylene blue reduction time and the rumen bacteria dry matter. Due to the easiness, promptness, feasibility, and its high sensibility the methylene blue reduction method should be used to check the ruminal profile.

Estudou-se o efeito da alimentação, do jejum e da realimentação sobre o perfil metabólico e ruminal de bovinos em crescimento. Para tal, empregaram-se 12 garrotes mestiços, com cerca de 300 kg, obtendo-se amostras de sangue e fluido ruminal no decorrer dos seguintes períodos: 11 horas de alimentação normal (período pós-prandial), 48 horas consecutivas de jejum alimentar, seguida de 48 horas de realimentação. Comparado com o período pós-prandial, o jejum provocou as seguintes modificações: moderada hipoglicemia; acompanhada por marcante lipólise, detectada pelo aumento nos teores plasmáticos de ácidos graxos livres; ausência de lipidose hepática, visto que não ocorreram alterações na atividade da aspartato aminotransferase e nos teores de colesterol sérico; discreta cetogênese, confirmada pela pequena elevação de β-hidroxibutirato; e certo grau de proteólise, verificado pelo aumento dos teores de uréia sérica e da excreção urinária de uréia. Nesse mesmo período ocorreu uma ligeira hipovolemia, caracterizada pelo aumento no déficit de volume intravascular. Este quadro metabólico verificado durante o jejum foi completamente revertido durante a realimentação, com exceção da proteólise que foi temporariamente maior. O jejum provocou notável modificação no perfil ruminal: intensa elevação no pH do fluido; diminuição marcante na flora e fauna que foi detectada, respectivamente, pela menor quantidade de matéria seca bacteriana e expressiva redução no número de protozoários; notória elevação no tempo de redução do azul de metileno; queda no índice de excreção urinária de alantoína, contudo sem alteração no índice de excreção urinária de ácido úrico. A realimentação promoveu completa e rápida recuperação das variáveis do perfil ruminal, com exceção do número de protozoários, que embora tenha se elevado, não atingiu os valores basais. A prova de redução de azul de metileno apresentou alta correlação positiva (r = 0,89) com a quantidade de matéria seca bacteriana. Devido à facilidade, rapidez e praticidade de ser conduzida e a alta sensibilidade indica-se a prova de redução do azul de metileno como teste de eleição na análise do perfil ruminal. / The effect of feeding, fasting and refeeding on metabolic and ruminal profile of steers was studied. Thus, blood and ruminal samples were drawn of twelve 300 kg crossbred steers throughout three different periods: 11 hour during normal feeding, 48 hour of fasting followed by the same time of refeeding. The fasting caused a moderate hypoglycemia, followed by marked lipolysis, detected by the high plasma free fatty acid concentration, but there was no evidence of hepatic lipidosis, since there were no changes in the activity of aspartate aminotransferase and serum cholesterol levels; a discrete ketogenesis occurred as there was a slight increase in the β-hidroxibutirate concentration; proteolysis were detected by the increase of serum and urinary excretion of urea. During the fasting the animals developed a slight hypovolemia detected by the increase of the plasma volume deficit. These metabolic changes were completely reversed during the refeeding, but the proteolysis had a temporary increase. The fasting gave rise to deeply changes in the ruminal profile, such as: increase in the rumen pH, reduction the number of rumen protozoa and bacteria, as seen by the low bacteria dry matter; increase in the methylene blue reduction time and lowering of the urinary excretion of allantoin, but no changes were seen in the uric acid urinary level. The refeeding made the rumen status return to normal, but the protozoa number that despite a slight increase was very far away from the basal standard. There was a high (r = 0.89) positive correlation between the methylene blue reduction time and the rumen bacteria dry matter. Due to the easiness, promptness, feasibility, and its high sensibility the methylene blue reduction method should be used to check the ruminal profile.

No description available.

Inledning: Uthållighetsträning definieras som den typ av träning där flertalet stora muskelgrupper används och är i behov av hjärt-kärlsystemets kapacitet för att transportera syre till musklerna. Att fasta innebär i de flesta studier att ingen typ av föda intas före träningspassen medan att inte fasta vanligtvis innebär att 90 minuter före ett träningspass intas en kolhydratrik måltid. Insulin är viktig i fett-, protein- och kolhydratmetabolismen samt i uppsamlingen av socker i blodet. Glykogen fungerar som en energireserv i skelettmusklerna. Fria fettsyror är viktiga för att ge energi till den cellulära metabolismen som ska kunna fortgå. Syfte: Syftet med denna studie var att ta reda på om kroppen påverkas på olika sätt av uthållighetsträning på fastande respektive icke-fastande mage vad gäller insulin, muskelglykogen samt fria fettsyror hos människor. Metod: Litteratursökning i OneSearch med sökorden training* AND fasted state där sex artiklar valdes ut. Cohen’s D användes för att ge studiernas resultat en effektstorlek. Konfidensintervall användes för att bestämma om studierna var statistiskt signifikanta. Resultat: Tre studier undersökte insulin där resultaten visade att samtliga grupper som inte fastade före träningspassen hade lägst koncentration av insulin i viloperioden efter eftertestet. Samtliga sex studier undersökte muskelglykogen där resultaten visade att koncentrationen av muskelglykogen var högst efter eftertestet i gruppen som fastade före träningspassen i fem av sex studier. Tre studier undersökte fria fettsyror där resultaten visade att koncentrationen av fria fettsyror var lägst i eftertestet i gruppen som fastade före träningspassen i två av tre studier. Diskussion: Träning i icke-fastat tillstånd leder till att glykogennivåerna sparas vilket i sin tur leder till att oxidationen av insulin ökar vilket resulterar i lägre koncentrationer av insulin efter eftertestet. Träning i fastat tillstånd resulterar i ökad koncentration av muskelglykogen till energiunderhåll samt högre nivåer av β-hydroxyacyl coenzym A dehydrogenas (β-HAD), citratsyntasaktiviteten (CS-aktiviteten) samt succinatdehydrogenasaktiviteten vilket leder till ökad muskulär oxidativ kapacitet. Intag av kolhydrater före ett träningspass leder till ökat glykogenbesparande vilket resulterar i lägre koncentrationer av muskelglykogen jämfört med icke-fastat tillstånd. Högre koncentration av muskelglykogen före förtestet leder till högre koncentrationer av muskelglykogen i eftertestet. Träning i fastat tillstånd resulterar i lägre koncentrationer av fria fettsyror på grund av ökad FATmax (den maximala hastigheten av fettförbränning), ökad maximal oxidativ enzymaktivitet, uppreglering av hormonkänsligt lipas (HSL), ökat proteinuttryck av fettsyra-translokas / CD36 (FAT / CD36) samt ökat membranbundet proteinbindande protein som leder till ökad fettförbränning. Koncentrationen av fria fettsyror höjdes även i en studie på grund av att insulinutsöndringen inte skulle sjunka för lågt i gruppen som fastade före träningspassen. Konklusion: Resultaten visade att i tre av tre studier var insulinkoncentrationen lägst efter eftertestet i gruppen som intog en kolhydratrik måltid före träningspassen. I fem av sex studier var koncentrationen av muskelglykogen högst efter eftertestet i gruppen som fastade före träningspassen. I två av tre studier var koncentrationen av fria fettsyror lägst efter eftertestet i gruppen som fastade före träningspassen. Dessa resultat ökar förståelsen av hur träning på fastande respektive icke-fastande mage påverkar kroppen med avseende på insulin, muskelglykogen samt fria fettsyror. Vidare forskning skulle kunna undersöka dessa tre fysiologiska markörer under sex månader för att se om resultaten blir desamma i dessa två grupper. / Introduction: Endurance training is defined as the type of exercise where most major muscle groups are used in need of the cardiovascular system’s ability to transport oxygen to the muscles. Fasting means in most studies that no type of food is taken before the workout while not fasting usually means that a carbohydrate meal is taken 90 minutes before a workout. Insulin is important in fat, protein and carbohydrate metabolism as well as in the collection of sugar in the blood. Glycogen acts as an energy reserve in the skeletal muscles. Free fatty acids are important to provide energy for the cellular metabolism that can continue. Aim of the study: The aim of the study was to find out if the body is affected in different ways by endurance training exerted in fasted respectively non-fasting state regarding insulin, muscle glycogen and free fatty acids in humans. Methods: Literature search in OneSearch with the words training* AND fasted state where six articles were selected. Cohen’s D was used to give the results of the studies an effect size. Confidence interval was used to determine if the studies were statistically significant. Results: Three studies investigated insulin, where the results showed that all groups that did not fast before the workouts had the lowest concentration of insulin during the rest period after the test. All six studies investigated muscle glycogen, where the results showed that the concentration of muscle glycogen was highest after post-test in the group that fasted before the workouts in five out of six studies. Three studies investigated free fatty acids where the results showed that the concentration of free fatty acids were lowest in the post-test in the group that fasted before the workouts in two of three studies. Discussion: Training in the non-fasting state causes the glycogen levels to be saved, which in turn leads to increased oxidation of insulin resulting in lower concentrations of insulin after the post-test. Training in the fasted state results in increased concentration of muscle glycogen for energy maintenance and higher levels of β-hydroxyacyl coenzyme A dehydrogenase (β-HAD), citrate synthase activity (CS activity) and succinate dehydrogenase activity, leading to increased muscular oxidative capacity. Intake of carbohydrates prior to a workout leads to increased glycogen saving, resulting in lower concentrations of muscle glycogen compared to non-fasted state. Higher concentration of muscle glycogen before the pretest leads to higher concentrations of muscle glycogen in the post-test. Training in fasted state results in lower concentrations of free fatty acids due to increased FATmax (maximum rate of fat burning), increased maximal oxidative enzyme activity, hormone sensitive lipase (HSL) upset, increased fatty acid translocase / CD36 protein expression (FAT / CD36) as well as increased membrane bound protein binding protein which leads to increased fat burning. The concentration of free fatty acids was also increased in a study due to the fact that insulin secretion should not fall too low in the group that fasted before the workouts. Conclusion: The results showed that in three out of three studies, the insulin concentration was lowest after the post-test in the group who took a carbohydrate meal before the workouts. In five out of six studies, the concentration of muscle glycogen was highest after the post-test in the group that fasted before the workouts. In two out of three studies, the concentration of free fatty acids was lowest after the post-test in the group that fasted before the workouts. These results increase the understanding of how exercise in the fasted state and non-fasted state affects the body with regard to insulin, muscle glycogen and free fatty acids. Further research could investigate these three physiological markers for six months to see if the results are the same in these two groups.

The intermittent fasting diet has a historical past, but recently, it has regained popularity as a weight loss strategy for the general public. Athletes have also picked up this specialized diet in search of a competitive edge. There are ample studies testing athletes of all levels, but most do not include females or report sex-specific results. This systematic review aimed to identify current research on the effects of intermittent fasting in the understudied population of female athletes. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted in three databases, including PubMed, Cochrane, and SPORTDiscus, and a total of six studies with experimental or observational designs testing the various effects of intermittent fasting on physical, physiological, and psychological parameters were included. This systematic review shows that studies found significant changes in calorie and fluid intake, body composition, nutrient utilization, well-being, and athletic performances with no changes in muscle strength, ratings of perceived exertion, blood lactate levels, and cognitive function. Multiple studies in this review found mixed results on changes in heart rate and athletic performance (vertical jump height), and no studies found negative effects on athletic performance except in the survey of athletes’ perceptions. Due to conflicting results of current research, more studies are needed to determine the effects of intermittent fasting combined with continuous exercise on athletic women.