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Relation between n-3 polyunsaturated fatty acids and cellular sensors of energetic state
Zouhar, Petr ; Flachs, Pavel (advisor) ; Pecina, Petr (referee)
The important factor in regulation of metabolic processes is regulatory proteins, which are able to react by feed-back to energetic state of the cell. Big attention is focused on the AMP activated kinase (AMPK) and NAD+ activated deacetylase SIRT1. These enzymes interact together and their stimulation increases mitochondrial biogenesis and fatty acid oxidation. Due to this it functions beneficially against the onset of obesity, insulin resistance and ageing. Fasting, exercise and some antidiabetogenic drugs act by these regulators. n-3 polyunsaturated fatty acids (PUFA) are also known because of their stimulative effects on mitochondrial biogenesis and -oxidation. Previous work of our group have showed that intake of higher dose of n-3 polyunsaturated fatty acids (PUFA) in diet lead to increase in activity of AMPK in white adipose tissue. New results presented in this thesis show that SIRT1 is essential for increase in expression of stimulators of -oxidation (PPAR etc) in response to n-3 PUFA in diet. n-3 PUFA futher improve the metabolic profile synergistically with calorie restriction probably through SIRT1.
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Influence of supplementation with n-3 polyunsaturated fatty acids on inflammatory markers in patients on long-term parenteral nutrition
Svěchová, Hana ; Novák, František (advisor) ; Meisnerová, Eva (referee)
SMOFLipid® is a commonly used fat emulsion for parenteral nutrition. We investigated how enrichment of SMOFLipid® with n-3 polyunsaturated fatty acids (PUFA) in a form of second fat emulsion, Omegaven® , changes fatty acid composition of total plasma phospholipids and erythrocyte phospholipids, cytokine concentrations in serum and in supernatant from in vitro whole blood culture stimulated with lipopolasaccharide (LPS) and we evaluated also changes in oxido- reductive balance. Eight patients on long-term home parenteral nutrition recieved both emulsions, SMOFLipid® (6 weeks) and SMOFLipid® +Omegaven® (4 weeks), one by one. We observed no significant differences in common laboratory and clinical parameters between these two types of diet. Enrichment of SMOFLipid® with Omegaven® led to an increase in eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) in total plasma phospholipids and there was also an increse in proportion of EPA in erythrocyte phospholipids, while proportion of DHA remained unchanged. These changes were in both phospholipids of plasma and erythrocyte compensated for a decrease in proportion of linoleic and arachidonic acid (n-6 PUFA). There were elevated IL-6 and TNF-α serum concentrations in patients after both diets. There was a decrease in IL-6 production by 36% with SMOFLipid®...
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Selected Nutrients in Etiology, Prevention and Treatment of Obesity
Sedláček, Pavel ; Müllerová, Dana (advisor) ; Rajdl, Daniel (referee) ; Fiala, Zdeněk (referee)
SELECTED NUTRIENTS IN ETIOLOGY, PREVENTION AND TREATMENT OF OBESITY The 21st century pandemic of obesity is given by to the obesitogenic environment that helps to develop a positive energy balance, where the energy intake of an individual chronically exceeds his energy need, ie energy expenditure. There is an increase in body weight by increased or abnormal body fat accumulation in the body. Preventing the development of obesity is aimed at achieving energy balance, in the case of existing overweight or obesity, the treatment lies in inducing and maintaining a negative energy balance for some time, ie stimulating energy expenditure and reducing energy intake. Selected diet determines not only energy intake, but its individual nutrients can also partially affect energy expenditure and fat tissue physiology. The aim of this work is to describe and experimentally verify some nutrients that could help in weight reduction and physiological function of adipose tissue. Based on the literature data, 19 active substances or mixtures were considered. A mixture of ω-3 polyunsaturated fatty acids (ω-3 PUFA), eicosapentaenoic acid and docosahexaenoic acid, in a daily dose of 0.6 g, in the form of fish oil in a certified food supplement was chosen as the most suitable for the experiment. In a 12-week, three-arm, parallel...
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Characterization of metabolic effects of dietary omega-3 fatty acids in transgenic PPARα-humanized mice
Kalendová, Veronika ; Rossmeisl, Martin (advisor) ; Šilhavý, Jan (referee)
Obesity is tightly connected with metabolic diseases including insulin resistance, type 2 diabetes or dyslipidemia. Peroxisome proliferator-activated receptor (PPAR)-α is a key transcription factor involved in the regulation of lipid metabolism, while its activity is stimulated by a variety of hypolipidemic drugs. n-3 polyunsaturated fatty acids (PUFA), including eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid, are endogenous ligands of PPARα, and they are used in the form of fish oil as dietary supplements in order to lower blood lipid levels and to prevent cardiovascular disease. Wax esters represent a novel lipid form of EPA and DHA, and according to recent studies they could exert more potent effects than the classical fish oil (i.e. triacylglycerols). Mice of the 129S1/SvImJ inbred strain were used in the present experiment, and included wild-type (WT) mice, as well as transgenic mice either with the exclusive expression of the human form of PPARα (hPPARα) or mice completely lacking PPARα (PPARα-KO). Mice were fed for 8 weeks the following diets: (i) a control low-fat diet, (ii) obesogenic high-fat diet (cHF), and (iii) the cHF diet supplemented with the n-3 PUFA concentrate in the form of wax esters isolated from marine zooplankton Calanus finmarchicus (ω3Cal). Mice were subjected to...
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The metabolism of an adipose tissue in mice with high-fat diet-induced obesity: the role of anatomical localization of the tissue and diet composition
Krsková, Kateřina ; Janovská, Petra (advisor) ; Behuliak, Michal (referee)
Regulation of the flow of fatty acids (FA) by futile cycle (TAG/FA cycle) in white adipose tissue (WAT) is an important mechanism of controlling metabolism of FA and therefore its regulation is in the interest of research as a possible therapeutic target in the treatment of obesity and insulin resistance. The study of the murine model suggests that the treatment of the n-3 PUFA with mild caloric restriction (CR) probably induces the TAG/FA cycle mainly in epididymal depot. It also reduces inflammation in WAT and the risk of cardiovascular diseases. We focused on monitoring the gene expression encoding key enzymes of the TAG/FA cycle (PEPCK, ATGL, HSL, DGAT1 and DGAT2) in dorzolumbar (DL), gonadal (GON) and mesenteric (MEZ) depot in a murine model C57BL/6 using qPCR. We were interested in the influence of the composition of fats in the diet, the influence of administration of n-3 PUFA with combination of 10% CR and the difference of gene expression among depots of WAT. The results indicate that the supplementation of high-fat diet with n-3 PUFA contributes mainly to reduction of gene expression for DGAT2 and the combination of n-3 PUFA and CR increases expression of genes influencing the TAG/FA cycle. In MEZ unlike GON and DL fat depot were no significant differences in gene expression, while the different...
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Influence of supplementation with n-3 polyunsaturated fatty acids on inflammatory markers in patients on long-term parenteral nutrition
Svěchová, Hana ; Novák, František (advisor) ; Meisnerová, Eva (referee)
SMOFLipid® is a commonly used fat emulsion for parenteral nutrition. We investigated how enrichment of SMOFLipid® with n-3 polyunsaturated fatty acids (PUFA) in a form of second fat emulsion, Omegaven® , changes fatty acid composition of total plasma phospholipids and erythrocyte phospholipids, cytokine concentrations in serum and in supernatant from in vitro whole blood culture stimulated with lipopolasaccharide (LPS) and we evaluated also changes in oxido- reductive balance. Eight patients on long-term home parenteral nutrition recieved both emulsions, SMOFLipid® (6 weeks) and SMOFLipid® +Omegaven® (4 weeks), one by one. We observed no significant differences in common laboratory and clinical parameters between these two types of diet. Enrichment of SMOFLipid® with Omegaven® led to an increase in eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) in total plasma phospholipids and there was also an increse in proportion of EPA in erythrocyte phospholipids, while proportion of DHA remained unchanged. These changes were in both phospholipids of plasma and erythrocyte compensated for a decrease in proportion of linoleic and arachidonic acid (n-6 PUFA). There were elevated IL-6 and TNF-α serum concentrations in patients after both diets. There was a decrease in IL-6 production by 36% with SMOFLipid®...
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Relation between n-3 polyunsaturated fatty acids and cellular sensors of energetic state
Zouhar, Petr ; Pecina, Petr (referee) ; Flachs, Pavel (advisor)
The important factor in regulation of metabolic processes is regulatory proteins, which are able to react by feed-back to energetic state of the cell. Big attention is focused on the AMP activated kinase (AMPK) and NAD+ activated deacetylase SIRT1. These enzymes interact together and their stimulation increases mitochondrial biogenesis and fatty acid oxidation. Due to this it functions beneficially against the onset of obesity, insulin resistance and ageing. Fasting, exercise and some antidiabetogenic drugs act by these regulators. n-3 polyunsaturated fatty acids (PUFA) are also known because of their stimulative effects on mitochondrial biogenesis and -oxidation. Previous work of our group have showed that intake of higher dose of n-3 polyunsaturated fatty acids (PUFA) in diet lead to increase in activity of AMPK in white adipose tissue. New results presented in this thesis show that SIRT1 is essential for increase in expression of stimulators of -oxidation (PPAR etc) in response to n-3 PUFA in diet. n-3 PUFA futher improve the metabolic profile synergistically with calorie restriction probably through SIRT1.
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