National Repository of Grey Literature 29 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
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.
Distribution of mitochondrial uncoupling proteins in selected tissues from mice and rat
Alán, Lukáš ; Ježek, Petr (advisor) ; Flachs, Pavel (referee)
Mitochondrial uncoupling proteins (UCPs) belong to the superfamily of mitochondrial anion-carriers. The longest known is UCP1, predominantly expressed in brown adipose tissue, where it takes part in nonshivering thermogenesis. In the late 1990s were discovered other sequence homologs of UCP1 with tissue specific distribution. The Function of these "new" uncoupling proteins is still uncertain. It is assumed that each of the isoforms has a specific function depending on the type of tissue. This thesis showed differences in tissue transcription pattern between rat and mice using RT-PCR absolute quantification. Significant differences in pattern were found in lungs, brain and muscle. In each case UCP expression was higher in mice tissues. Mice lungs express mainly UCP2. The difference in mice brain is caused by ucp4 and ucp5 genes transcription and finally in muscle is highest content of UCP3 mRNA. We investigated whether any of ucp transcript can complement ucp2 transcripton in spleen or lungs of ucp2 -/- mice. We did not find any difference which can explain, that in isolated lung mitochondria of fasted ucp2-/- mice were uncoupled in state 4. In the last project, we found relationship between ucp2 transcription in insulinoma INS-1E cells and oxygen levels of the cultivation atmosphere.
New regulatory metabolic factors in patients with obesity and type 2 diabetes mellitus
Matějková, Mirka ; Haluzík, Martin (advisor) ; Flachs, Pavel (referee)
Fibroblast growth factors are proteins with diverse biological function in development, tissue repair, and metabolism. The human FGF gene family consists of 22 members. FGF 19 subfamily includes FGF 19, FGF 21, and FGF 23. They act as systemic factors in an endocrine manner. FGF 19 subfamily requires klotho protein as a cofactor for its action. FGF 19 produced by intestine acts mainly in the liver through FGFR4, where it inhibits bile acid and fatty acid synthesis. FGF 21 is produced by the liver and contributes to the regulation of carbohydrate and lipid metabolism through modulation of glucose uptake in adipocytes. Serum FGF 21 levels are increased in patients with obesity and type 2 diabetes mellitus. Serum FGF 19 levels are on the contrary decreased in patients with obesity and type 2 diabetes mellitus and more probably depend on the nutritional status of the organism than on the glucose metabolism and insulin sensitivity. Key words: type 2 diabetes mellitus, FGF 19, FGF 21, obesity, adipose tissue
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...
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
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...
Molecular adaptations of adipose tissue in relation to dietary treatment of obesity in human
Tencerová, Michaela ; Štich, Vladimír (advisor) ; Flachs, Pavel (referee) ; Kazdová, Ludmila (referee) ; Kunešová, Marie (referee)
The general goal of this work was to investigate the molecular adaptations of human AT in relation to DIs with respect to its secretory activity as well as cellular composition focused on macrophages population. Specifically, we studied the role of novel adipokines, such as visfatin and RBP4, related to insulin resistance and AT metabolism. Furthermore, we wanted to characterize the effect of the dietary-induced changes on the content of ATM together with metabolic amelioration. In our studies, we found that lifestyle modifications had a beneficial effect on metabolic and biochemical parameters depending on the duration and type of DI. Regarding both of the investigated adipokines, visfatin and RBP4, we revealed modifications at the transcriptional and cirulating levels during DI. However, we did not find any association with the pattern of evolution of insulin resistance. Our findings do not support a clear hypothesis on the role of these adipokines in the diet-induced improvement of insulin sensitivity and other obesity-related metabolic disturbances. In respect to the changes of ATM content during long-term DI, we demonstrated using flow cytometry that the AT composition was changed at the end of the whole dietary intervention (i.e. after WM phase). This diet-induced AT remodelling was expressed by a...
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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