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Characterization of energy metabolism of murine models of obesity
Irodenko, Ilariia ; Bardová, Kristina (advisor) ; Šilhavý, Jan (referee)
Energy metabolism involves processes of energy intake and energy expenditure, including storage of excessive energy in a form of lipids. White adipose tissue stores energy and plays an important role in maintenance of energy homeostasis. Animals obtain energy by oxidation of substrates from diet. Indirect calorimetry is a method for assessment of energy expenditure based on a measurement of oxygen consumption and carbon dioxide production. The VCO2/VO2 ratio (Respiratory Quotient) indicates oxidation of specific metabolic substrates. Metabolic flexibility is the ability of an organism to match substrate oxidation to its availability. The decrease of a metabolic flexibility is linked to inability to adapt to available substrate and with excessive lipid storage in the body. In this thesis we evaluated correlation between the metabolic flexibility defined by indirect calorimetry and the adipose tissue metabolism in two strains of mice, C57Bl/6J and AJ, that differ in their propensity to diet-induced obesity. Increased whole-body metabolic flexibility in A/J mice was connected to higher ability of adipose tissue to release and uptake lipids. The study of reaction to high-fat diet enables us to distinguish "metabolically healthy" and "metabolically unhealthy" adipose tissue. The knowlegde of these...
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Utilization of energy substrates in white and brown adipose tissue in metabolic syndrome
Seďová, Karolína ; Škop, Vojtěch (advisor) ; Šilhavý, Jan (referee)
1 Abstrakt Hnědá tuková tkáň je unikátní termoregulační orgán, její funkcí je přeměňovat energii ve formě protonového gradientu na energii tepelnou a zároveň snižovat efektivitu metabolismu. Její funkce se zdá být nadějí v léčbě metabolického syndromu a komplikací s ním spojených. Efekt hnědé tukové tkáně v léčbě MS však stále není objasněn a proto jsme chirurgicky odstranili tuto tkáň u potkanů, kteří trpí metabolickým syndromem, abychom objasnili důsledky extirpace na parametry metabolického syndromu. V této práci jsme sledovali aktivitu interskapulární tukové tkáně na parametry metabolického syndromu. Srovnávali jsme parametry mezi kmeny HHTg potkanů a kontrolním kmenem potkanů Wistar a pozorovali jsme nižší hmotnost potkanů kmene HHTg přes projevy ostatních parametrů metabolického syndromu, jako je dyslipidémie, inzulinová rezistence tukové tkáně, vyšší hodnoty NEMK v krvi. Zjistili jsme, že tito potkani mají významně vyšší aktivitu iBAT, jak v inkorporaci palmitátu do lipidů, tak ve spalování lipidů ve formě CO2 a zejména v nižším věku. Tato zjištění nás vedla k hypotéze, že iBAT by mohla mít zásadní vliv na parametry MS u neobézních potkanů. Extirpací iBAT u mladých potkanů, ani u potkanů v pokročilejším věku však neměla zásadní vliv na metabolismus ani na hmotnost. Dokonce došlo ke zlepšení některých...
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Regulation of lipolysis and re-esterification in white adipose tissue - possible role of FGF21
Špiláková, Blanka ; Zouhar, Petr (advisor) ; Šilhavý, Jan (referee)
Fibroblast growth factor 21 (FGF21) is a unique peptide hormone involved in the energy homeosta- sis, as well as in the regulation of glucose and lipid metabolism. Numerous animal studies suggest that FGF21 may be used as a potential treatment for obesity and type 2 diabetes mellitus. It was found out, that FGF21 counteracts the development of obesity presumably by increasing energy expenditure through activation of thermogenesis in brown and white adipose tissue. FGF21 apparently also inhibits lipolysis. However, the specific mechanism of action of FGF21 is not clear. In our experiments we studied the antiobesogenic effects of FGF21 on mice model of diet-induced obesity at thermoneutrality. It is assumed that this model approach (in contrast to housing mice at standard laboratory temperature) mimics closely the metabolic status of humans. During the 4- to 8-day FGF21 treatment we observed a gradual reduction of lipid content in the brown and white adipose tissue and liver, especially in combination with β3-adrenergic stimulation. We have confirmed that FGF21 inhib- its lipolysis and also stimulates browning in certain adipose tissue depots. Furthermore, we have found that the effect of FGF21 on fatty acid secretion by adipose tissue is not mediated by changes in the fatty acid re-esterification...
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Cardioprotective action of ischemic perconditioning
Chalupová, Miloslava ; Neckář, Jan (advisor) ; Šilhavý, Jan (referee)
Remote ischemic perconditioning (RIPerC) is acknowledged to be a promising cardioprotective strategy, defined as brief repetitive periods of ischemia and reperfusion applied during ongoing myocardial infarction. This method provides protection against ischemia-reperfusion injury. Although remote perconditioning reduces infarct size, the underlying mechanisms remain unclear. The aim of this thesis is to summarize the current knowledge of RIPerC, its molecular mechanisms and protective effects on the heart.
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Characterization of energy metabolism of murine models of obesity
Irodenko, Ilariia ; Bardová, Kristina (advisor) ; Šilhavý, Jan (referee)
Energy metabolism involves processes of energy intake and energy expenditure, including storage of excessive energy in a form of lipids. White adipose tissue stores energy and plays an important role in maintenance of energy homeostasis. Animals obtain energy by oxidation of substrates from diet. Indirect calorimetry is a method for assessment of energy expenditure based on a measurement of oxygen consumption and carbon dioxide production. The VCO2/VO2 ratio (Respiratory Quotient) indicates oxidation of specific metabolic substrates. Metabolic flexibility is the ability of an organism to match substrate oxidation to its availability. The decrease of a metabolic flexibility is linked to inability to adapt to available substrate and with excessive lipid storage in the body. In this thesis we evaluated correlation between the metabolic flexibility defined by indirect calorimetry and the adipose tissue metabolism in two strains of mice, C57Bl/6J and AJ, that differ in their propensity to diet-induced obesity. Increased whole-body metabolic flexibility in A/J mice was connected to higher ability of adipose tissue to release and uptake lipids. The study of reaction to high-fat diet enables us to distinguish "metabolically healthy" and "metabolically unhealthy" adipose tissue. The knowlegde of these...
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Regulation of lipolysis and re-esterification in white adipose tissue - possible role of FGF21
Špiláková, Blanka ; Zouhar, Petr (advisor) ; Šilhavý, Jan (referee)
Fibroblast growth factor 21 (FGF21) is a unique peptide hormone involved in the energy homeosta- sis, as well as in the regulation of glucose and lipid metabolism. Numerous animal studies suggest that FGF21 may be used as a potential treatment for obesity and type 2 diabetes mellitus. It was found out, that FGF21 counteracts the development of obesity presumably by increasing energy expenditure through activation of thermogenesis in brown and white adipose tissue. FGF21 apparently also inhibits lipolysis. However, the specific mechanism of action of FGF21 is not clear. In our experiments we studied the antiobesogenic effects of FGF21 on mice model of diet-induced obesity at thermoneutrality. It is assumed that this model approach (in contrast to housing mice at standard laboratory temperature) mimics closely the metabolic status of humans. During the 4- to 8-day FGF21 treatment we observed a gradual reduction of lipid content in the brown and white adipose tissue and liver, especially in combination with β3-adrenergic stimulation. We have confirmed that FGF21 inhib- its lipolysis and also stimulates browning in certain adipose tissue depots. Furthermore, we have found that the effect of FGF21 on fatty acid secretion by adipose tissue is not mediated by changes in the fatty acid re-esterification...
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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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Utilization of energy substrates in white and brown adipose tissue in metabolic syndrome
Seďová, Karolína ; Škop, Vojtěch (advisor) ; Šilhavý, Jan (referee)
1 Abstrakt Hnědá tuková tkáň je unikátní termoregulační orgán, její funkcí je přeměňovat energii ve formě protonového gradientu na energii tepelnou a zároveň snižovat efektivitu metabolismu. Její funkce se zdá být nadějí v léčbě metabolického syndromu a komplikací s ním spojených. Efekt hnědé tukové tkáně v léčbě MS však stále není objasněn a proto jsme chirurgicky odstranili tuto tkáň u potkanů, kteří trpí metabolickým syndromem, abychom objasnili důsledky extirpace na parametry metabolického syndromu. V této práci jsme sledovali aktivitu interskapulární tukové tkáně na parametry metabolického syndromu. Srovnávali jsme parametry mezi kmeny HHTg potkanů a kontrolním kmenem potkanů Wistar a pozorovali jsme nižší hmotnost potkanů kmene HHTg přes projevy ostatních parametrů metabolického syndromu, jako je dyslipidémie, inzulinová rezistence tukové tkáně, vyšší hodnoty NEMK v krvi. Zjistili jsme, že tito potkani mají významně vyšší aktivitu iBAT, jak v inkorporaci palmitátu do lipidů, tak ve spalování lipidů ve formě CO2 a zejména v nižším věku. Tato zjištění nás vedla k hypotéze, že iBAT by mohla mít zásadní vliv na parametry MS u neobézních potkanů. Extirpací iBAT u mladých potkanů, ani u potkanů v pokročilejším věku však neměla zásadní vliv na metabolismus ani na hmotnost. Dokonce došlo ke zlepšení některých...
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