Browsing by Subject "rasvamaksa"

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  • Purhonen, Janne (Helsingin yliopisto, 2015)
    GRACILE syndrome (Fellman disease) is a neonatal mitochondrial disorder with hepatopathy belonging to Finnish disease heritage. The GRACILE acronym comes from the most important clinical features of the disorder: fetal growth restriction, aminoaciduria, cholestasis (with steatosis and fibrosis), hepatic iron overload, lactic acidosis, and early death during infancy. The syndrome is caused by mutated (homoyzygous c.232A>G) BCS1L, a nuclear gene encoding a respiratory chain complex III assembly factor. BCS1L mutations compromise Rieske iron-sulfur protein incorporation into complex III, which leads to respiratory chain deficiency. Bcs1l c.232A>G knock-in C57BL/6 mouse model mimics the human disorder, and the homozygous mice (GRACILE mice) display growth restriction, progressive liver disease and a short life span. For a vast majority of mitochondrial disorders no effective treatments currently exist. One promising treatment strategy is to increase mitochondrial biogenesis with the idea that respiratory chain deficiency can be compensated by boosting mitochondrial function. In mouse models of mitochondrial myopathies induction of mitochondrial biogenesis with a transgene approach, pharmaceutical intervention or ketogenic diet has alleviated the disease. It has been hypothesized that ketogenic diet activates energy deprivation signals of the cells, which are the most important regulators of mitochondrial biogenesis. So far ketogenic diet has not been studied in animal models of mitochondrial hepatopathies. The objective of this master’s thesis was to study effect of ketogenic diet on hepatopathy of GRACILE mouse model. From weaning on, wild-type and homozygous mutant mice (n = 11 - 14 per group) were fed standard chow or ketogenic diet (90,5 E% fat) for three weeks after which the mice were sacrificed and tissues collected for analysis. The effect of ketogenic diet was evaluated with following methods: liver histology (H&E, Sirius Red, Oil Red O, PAS and semiquantitative scoring), liver triglyceride content, mitochondrial DNA copy number (qPCR), expression of selected genes (qPCR) and respiratory chain proteins (Western blot). The mice tolerated the ketogenic diet, and the diet did not affect weight gain. Livers of wild-type mice on ketogenic diet were considered normal except for slight fat accumulation. In GRACILE mice ketogenic diet ameliorated some aspects of the liver disease (less signs of inflammation and fibrosis) but increased microvesicular steatosis. Mitochondrial DNA copy number was unchanged among groups. Ketogenic diet did not affect gene or protein expression of selected respiratory chain components. The GRACILE mutation increased gene expression of Pgc1a, a gene encoding a master regulator of mitochondrial biogenesis, as well as protein and mRNA levels of respiratory chain complex IV subunits. The ketogenic diet had a clear effect on liver phenotype in the mutant mice, but a longer follow-up time is needed to show the effect on disease progression. The beneficial action of ketogenic diet on liver histology might not be related to increased number of mitochondria or respiratory chain proteins, and the mechanism behind the effect need to be elucidated in further investigations.
  • Rechardt, Ilona (Helsingfors universitet, 2016)
    Introduction: Abundant proportion of added sugar in the diet of children predisposes to overweight and impairs the overall quality of the diet. In particular, the consumption of sugar-sweetened soft drinks has been linked to the increased incidence of overweight and obesity in children and more recently to the increased incidence of fatty liver. However, with respect to consumption of other foods rich in added sugar the research data is insufficient. As the growing number of population is becoming overweight/obese the prevalence of fatty liver is increasing in children as well, and it is important to find out the significance of added sugar intake in childhood with respect to the risk of fatty liver in adulthood. Objective: The objective of this study is to determine the main sources and consumption of added sugar in the diets of 3-18 year-old children and to examine the stability of the consumption from childhood to adulthood. In addition, the objective is to examine the association between the consumption of foods containing added sugar and the risk of fatty liver in the longitudinal setting. Materials and methods: The data used in this thesis is based on the ongoing Cardiovascular Risk in Young Finns study collected during 1980-2011. The study population is comprised of the diet records of 3597 3-18 year-old children and adolescents participated in 1980. In addition, liver ultrasound was performed in 2011 for determining fatty liver prevalence. Indicator foods which best explain the variation in the intake of added sugar were determined by linear regression analysis and converted into monthly portions. The stability of sugar intake was studied by dividing the data into quarters and examining the proportion of people staying in the same group. The long-term average use of indicator foods was compared in the fatty liver classes with T-test, which illustrates the cumulative intake of added sugar and its possible link to the risk of fatty liver. In addition, the probability of fatty liver with respect to the consumption categories of indicator foods was analysed with logistic regression analysis. Finally, the relation of each indicator foods and total energy intake was examined with trend analysis. Results: In this thesis, the indicator foods selected were sweets, ice cream, soft drinks, yogurt and sweet bakery products. In all the study years, the use of these foods explained the variation in the intake of added sugar from one third to three quarters. There were also clear stability (tracking) observed in the use of these foods. However, the long-term use of these foods was not connected to the risk of fatty liver in a cumulative manner. The average number of portions per month in healthy subjects was 44.6 (SD 16.9) and in fatty liver patients 43.1 (SD 17.4), and the difference between groups was not statistically significant (p 0.133). However, individually examined the use of soft drinks significantly increased the probability of fatty liver (OR 2.24 [95% CI 1.45–3,44]) when compared the group using the most soft drinks with the group using the least. In contrast, consumption of sweets during some years was connected with a lower probability of fatty liver (OR 0.57 [95% CI 0.34–0,97]). Furthermore, based on trend analysis the total energy intake increased by the consumption of soft drink quartiles (p <0.0001), which was not seen with other indicator foods. Conclusion: There was clear stability in the use of the indicator foods in this Master's Thesis during the 27 year study period. Those subjects who 1980 ate the most sugar containing foods, did so at a later stage in their lives. However, the use was not related in the risk of fatty liver in a cumulative manner. However, the consumption of sugar-sweetened soft drinks in adulthood increased the risk of fatty liver significantly. A similar relationship was not observed with the intake of soft drinks in childhood, sweets, ice cream, sweet bakery products or yogurt. The reason for this most likely lies in the total energy intake, because the more the subjects drank sugar-sweetened soft drinks, the greater was their energy intake.