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Effect of fatty acids on lipid metabolism and weight reduction
Hlavatý, Petr ; Kunešová, Marie (advisor) ; Müllerová, Dana (referee) ; Flachs, Pavel (referee)
Fat tissue plays a main role in the development of the metabolic syndrome. Many components of the metabolic syndrome may be improved by dietary arrangements, including an increased intake of n-3 PUFA. In addition to the positive effect of n-3 PUFA, a possible effect of a higher calcium intake on influencing weight loss and energy metabolism has also been discussed for a long time. In addition to nutritional factors, genetic factors significantly contribute to influencing weight and lipid and glucose metabolism. In study A, 40 obese women were observed during three weeks of weight reduction management. Women were randomly divided into two groups. The first group received yogurt enriched with n-3 PUFA, and the second group consumed yoghurt without the supplementation. The results show that low-dose supplementation with n-3 PUFA in yogurt in combination with a reduced energy intake increases n-3 PUFA content in serum lipids and prevents adverse changes in the composition of FA in serum after a short-term low-calorie diet. In study B, we monitored the influence of n-3 PUFA supplementation on short-term weight management with VLCD in 20 women with severe obesity, who were randomly divided into two groups. The first group received VLCD enriched with n-3 PUFA, the second group VLCD with a placebo. The addition of...
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The role of plasma membrane Na+/H+ antiporters in the physiology of yeast cells
Papoušková, Klára ; Sychrová, Hana (advisor) ; Hašek, Jiří (referee) ; Flachs, Pavel (referee)
) r Nhal-type antiporterswith differentsubstratespeciÍicity(or affinityto individualsubstrates) andfunctions.One of themis involvedin thedetoxificationof cells andtheothercouldplay an importantrole in the maintenanceof stableintracellularpotassiumcontent,cell volume andpH of thecýoplasmthanlsto its abilitytotransportK+. At this time, no yeast speciespossessingsolely a Na*/fI*antiporterwith narrow substratespecificity (for Na* and Li) is known;therefore,the physiologicalrole of Nhal- type antiportersseemsto be complexwith a participationboth in the eliminationof toxic cationsfromcells andin themaintenanceof stableintracellularK* concentration,cell volume andcýoplasmic pH. 4.Summary Themainresultsof thethesíscanbesummarizedas: o The studiesof sequencesof yeastalkali metalcation/Iťantiporters(Nhal, Nhxl andKhal families)in silico showedthatthe structureof all threegroupsof theseproteinsprobably contains 12 transmembranesegments,we found some conservedamino acid residuesor motifslikely to be importantforproperfunctioningof antiporters,andourphylogeneticstudy revealedthatNhxl proteinsare relatedto both plant and mammalianNa*/Iť antiporters, Khal antiportersare close to thebacterialrelativesandNhal-type proteinsform a soparate goup so far characteizedonly in yeastsor fungi. o The D. hanseniiNHAI geneencodesa...
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Effect of biguanides on liver cells metabolism
Švecová, Eliška ; Kalous, Martin (advisor) ; Flachs, Pavel (referee) ; Hansíková, Hana (referee)
The extract from the plant Galega officinalis containing the guanidine derivative galegin has been used in the treatment of diabetes-associated complications since middle ages. Nevertheless, the positive effects of the treatment were often overweight by the adverse side effects. Some sixty years ago guanidin was replaced by the less toxic synthetic biguanide derivatives - metformin, phenphormin and buformin, the latter two being withdrawn due to the unacceptable risk of fatal lactate acidosis. Metformin is still widely used antidiabetics and belongs to the first choice drugs in the treatment of type 2 diabetes. Phenphormin is now gaining renewed attention with regard to its antineoplastic properties. Despite its long-term clinical use the mechanism of biguanides action is not fully understood yet. At present it is generally accepted that the core of its antihyperglycemic effect lays in the inhibition of hepatic gluconeogenesis. In contrast, there is less consensus regarding the particular metabolic pathway or target that are responsible for the metformin-induced attenuation of gluconeogenesis. For a long time, a hot candidate for metformin target in the cell was AMP-activated kinase (AMPK) but the metformin effect was proved also in mice carrying the dominant negative mutation of AMPK α subunit. Quite...
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Genetic and functional characterisation of mitochondrial diseases caused by ATP synthase defects
Tauchmannová, Kateřina ; Houštěk, Josef (advisor) ; Flachs, Pavel (referee) ; Kutejová, Eva (referee)
Disorders of ATP synthase, the key enzyme of mitochondrial energy provision belong to the most severe metabolic diseases presenting mostly as early-onset mitochondrial encephalo-cardio-myopathies. Mutations in four nuclear genes can result in isolated deficiency of ATP synthase, all sharing a similar biochemical phenotype - pronounced decrease in the content of fully assembled and functional ATP synthase complex. The thesis summarises studies on two distinct causes of ATP synthase deficiency. First is TMEM70 protein, a novel ancillary factor of ATP synthase, which represents most frequent determinant of severe inborn deficiency of ATP synthase. TMEM70 is a 21 kDa protein of the inner mitochondrial membrane, facilitating the biogenesis of mitochondrial ATP synthase, possibly through TMEM70 protein region exposed to the mitochondrial matrix, but the proper regulatory mechanism remains to be elucidated. In TMEM70-lacking patient fibroblasts the low content of ATP synthase induces compensatory adaptive upregulation of mitochondrial respiratory chain complexes III and IV, interestingly by a posttranscriptional mechanisms. The second type of ATP synthase deficiency studied was mtDNA m.9205delTA mutation affecting maturation of MT-ATP8/MT-ATP6/MT-CO3 mRNA and thus biosynthesis of Atp6 (subunit a) and Cox3...
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Physiological relevance of futile cycling based on lipolysis and fatty acid re-esterification in white adipose tissue
Funda, Jiří ; Flachs, Pavel (advisor) ; Kolář, David (referee)
AJ The thesis deals with the task of futile metabolic cycling, mainly on the cycle including lipolysis and fatty acid re-esterification, which takes place in white adipose tissue. This cycle plays some essential roles in organism, including regulation of important metabolic pathways in lipid metabolism and also exhibit certain influence on the whole body energy metabolism. First part of the thesis is focused on general properties of futile metabolic cycles and shows some examples of their functions in organism. Next part presents detail view on single steps making the whole lipolysis/re-esterification cycle. Considerable part deals with the ways of regulation of futile cycle activity. This approach may increase an impact of futile cycling on processes under its influence. Physiological relevance of futile metabolic cycle based on lipolysis and fatty acid re-esterification in white adipose tissue was described in numerous studies. This thesis shows their results for a purpose to provide a summary of functions of this system in physiology of mammals. Key words futile metabolic cycle, lipolysis, re-esterification, fatty acids, adipose tissue
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Effects of selected biologically active natural compounds on mammalian energy metabolism
Seďová, Karolína ; Flachs, Pavel (advisor) ; Doleželová, Šárka (referee)
Obesity is associated with many diseases, particularly type 2 diabetes, hypertension, dyslipidemia , hyperglycemia and cardiovascular diseases. If a patient experiences at least a trio of these diseases are diagnosed metabolic syndrome. The prevalence of obesity and related diseases has increased at an alarming rate in recent years and has become a worldwide health problem. Cardiovascular disease is the leading cause of death worldwide. Some minor components which are commonly found in our diet (eg some plant metabolites), directly or indirectly affect energy metabolism of our body and thus can reduce or even prevent developing health complications associated with the metabolic syndrome. This thesis, aims to clearly summarize the findings and results of scientific studies on selected plant metabolites occurring in extracts of specific plants that have preventive or therapeutic effects on obesity and other components of the metabolic syndrome. This work describes the use of these substances in the pharmaceutical industry and the food industry, the primary natural resources , and mechanisms of action , including effective doses. Powered by TCPDF (www.tcpdf.org)
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Importance of adipose tissue metabolism for whole-body energy balance
Zouhar, Petr ; Flachs, Pavel (advisor) ; Rossmeislová, Lenka (referee) ; Kazdová, Ludmila (referee)
Adipose tissue plays a crucial role in nutrient and energy homeostasis. At the time of worldwide pandemy of obesity and consequent metabolic syndrome, a great effort is made to find new treatments with potential to preserve insulin sensitivity, or even counteract development of obesity and type 2 diabetes. There are three principal possibilities how the adipose tissue biology can contribute to this goal: 1) induction of UCP1-dependent energy dissipation in brown adipose tissue; 2) conversion of white adipose depots to brown-like tissue (i.e. "browning"); and 3) stimulation of UCP1-independent thermogenesis in white adipose tissue. This thesis is based on two published works and one article under preparation. Generaly, it is focused on three different approaches targeting the above mentioned processes in adipose tissue of laboratory mouse: 1) diet supplementation with bile acids; 2) combination treatment of ω-3 polyunsaturated fatty acids and calorie restriction; and 3) cold exposure. In the experiments with administration of bile (specifically chenodeoxycholic) acid to mice, we confirm specific induction of UCP1 in both brown and subcutaneous white adipose tissue, as well as reversion of obesity in the response to the treatment. Nevertheless, most of the acute beneficial effects are mediated by...
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Amelioration of obesity-associated disorders by n-3 PUFA and oleuropein: adipocentric view
Svobodová, Michaela ; Flachs, Pavel (advisor) ; Cahová, Monika (referee) ; Kunešová, Marie (referee)
Charles University in Prague Faculty of Science Department of Genetics and Microbiology Academy of Sciences of the Czech Republic Institute of Physiology, v.v.i Synopsis of Ph.D. Thesis Amelioration of obesity -associated disorders by n-3 PUFA and oleuropein: adipocentric view Michaela Svobodová Praha 2015 Doktorské studijní programy v biomedicine 1 2 Univerzita Karlova v Praze a Akademie věd České republiky Program: Molekulární a buněčná biologie, genetika a virologie Předseda oborové rady: prof. RNDr. Stanislav Zadražil, DrSc. Školicí pracoviště: Fyziologický ústav AV ČR, v.v.i. Autor: Michaela Svobodová Školitel: RNDr. Pavel Flachs, Ph.D. S disertací je možno se seznámit v příslušných knihovnách Přírodovědecké fakulty Univerzity Karlovy v Praze.
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Interaction between adipocytes and immune cells in pathogenesis of obesity related pro-inflammatory state of adipose tissue
Mališová, Lucia ; Rossmeislová, Lenka (advisor) ; Flachs, Pavel (referee) ; Kazdová, Ludmila (referee)
Obesity is considered to be a worldwide epidemic disease characterized by an accumulation of AT. Increased adiposity can perturb normal metabolic functions and lead to the development of diseases like insulin resistance and other metabolic disorders. A large amount of clinical studies have been shown that changes in inflammatory signaling in adipose tissue cells, increased infiltration of immune cells into AT as well as stress of endoplasmic reticulum belong to the key molecular steps leading to the development of metabolic disturbances associated with this disease. Adverse metabolic effects of AT accumulation can be diminished by calorie restriction resulting in weight loss. In addition, stress of endoplasmic reticulum could be alleviated by chemical chaperones including bile acids. These two approaches for the treatment of obesity or the obesity-associated disturbances were basis for this PhD thesis. In the first part of this work, we studied inflammation status of gluteal in comparison with abdominal AT and differentiation and secretory capacity of adipocytes after weight loss in obese patients. We revealed that inflammatory profile of gluteal AT, estimated by mRNA level of macrophages and cytokines as markers of inflammatory status of the body, did not explain the different clinical impact of...
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