|
|
New pharmacological interventions influencing food intake focused on effects of CART (cocaine- and amphetamine-regulated transcript) peptide and prolactin-releasing peptide
Maixnerová, Jana ; Maletínská, Lenka (advisor) ; Zorad, Štefan (referee) ; Skálová, Lenka (referee)
The thesis was focused on characterization of biological activities of two recently discovered anorexigenic neuropeptides: CART (cocaine- and amphetamine-regulated transcript) peptide and prolactin-releasing peptide (PrRP). In order to find a pharmacophore of CART peptide, shorter fragments of CART(61- 102) peptide were tested for binding to PC12 cells and inhibition of food intake in fasted mice. The results showed that a compact structure of CART peptide containing three disulphide bridges is necessary for preservation of its full biological activity. In the second part of the thesis, synergistic and long-lasting effect of centrally administered peptide CART and peripherally administered cholecystokinin (CCK) is described. In fasted C57BL/6 mice, the anorexigenic effect of CART was enhanced by a subthreshold dose of CCK, while CCK1 receptor antagonist devazepide blocked the effect of CART peptide on food intake. In the third part of the thesis, food intake in fed lean and MSG (monosodiumglutamate treated) obese male mice with lesions in nucleus arcuatus (ARC) was followed. Anorexigenic action of CART peptide was preserved but satiety effect of CCK was completely lost in MSG obese mice and therefore, effective leptin signaling in ARC is necessary for satiety effect of CCK. Finally, the PrRP...
|
|
|
Impact of leptin and ghrelin on food intake and metabolic parameters in obese ovariectomized female mice
Matyšková, Resha ; Maletínská, Lenka (advisor) ; Jurčovičová, Jana (referee) ; Kuneš, Jaroslav (referee)
The thesis is focused on the effect of leptin and ghrelin receptor antagonists on food intake and metabolic parameters in ovariectomized (OVX) female mice on a high fat (HF) diet. In the first part of the thesis, diet-induced obesity was introduced in two strains of mice (NMRI and C57BL/6). Diet-induced obesity resulted from overconsumption of a HF diet containing 60 % of fat; a standard (St) diet contained only 9 % of fat. The strain C57BL/6 was more susceptible to a HF diet than the NMRI strain and was chosen for further experiments on food intake. In the second part of the thesis, OVX C57BL/6 female mice on a HF diet were introduced as a model of common obesity in women after menopause and overconsumption of high caloric food. OVX mice on a HF diet accumulated more than 4 times higher amount of the white adipose tissue compared to those on a St diet, had significantly elevated glucose, insulin and leptin levels and attenuated sensitivity to effect of centrally administered leptin, an adipokine that decreases food intake. Central leptin sensitivity and metabolic syndrome parameters were improved after 4 weeks of estradiol treatment. Because both ovariectomy and HF diet result in enhanced sensitivity to ghrelin, the hormone produced predominantly by the stomach that stimulates appetite, in the...
|
|
|
Peptide hormones affecting the food intake and their analogs as potential drugs for treatment of obesity
Nagelová, Veronika ; Maletínská, Lenka (advisor) ; Vybíral, Stanislav (referee)
Obesity is nowadays a major global health problem. Every year amount of obese (BMI > 30 kg . m-2 ) and overweight (BMI > 25 kg . m-2 ) people increases. Obesity is not just a cosmetic problem, but it leads to many serious health complications, particularly cardiovascular diseases, metabolic diseases etc. We can define obesity as an excessive amount of body fat. The development of obesity is often influenced by energy intake, which overrides the energy expenditure. Many studies are currently describe the influence of various substances that could potentially act as antiobesity drugs. Peptide hormones, which are engaged in this work, can be divided to the long-term (leptin, insulin, ghrelin) and short-term (e.g. cholecystokinin, glucagon like peptide 1, peptide YY, CART peptides, melanocortin system, neuropeptide Y and melanin concentrating hormone) acting. Peptides can be also divided according to their effect on food intake to the anorexigenic and orexigenic. Anorexigenic peptides reduce food intake, orexigenic do the reverse.
|
|
| |
|
| |
|
|
Mass Spectrometry Imaging of Metformin in Tissue Sections
Strnad, Štěpán ; Sýkora, D. ; Vrkoslav, Vladimír ; Cvačka, Josef ; Maletínská, Lenka ; Pirník, Zdenko
Mass spectrometry imaging is a powerful technique suitable for visualization of the distribution of a wide variety of compounds within tissue sections. The main aim of the study was the development and optimization of a sample preparation procedure allowing determination of the distribution of orally dosed metformin in mice kidney sections. Metformin is the first-line medication for the treatment of type 2 diabetes. The optimization of the sample preparation step before imaging experiments included the selection of a suitable matrix and the optimization of various parameters of MALDI analysis. 2,5-dihydroxybenzoic acid was identified as the best matrix providing highest sensitivity. A sublimation method was successfully used for the matrix deposition. The highest relative concentration of metformin was found in the inner zone of kidney 30 minutes after the drug administration.
|
|
|
Specific binding of prolactin-releasing peptide analogues in pituitary cells
Maixnerová, Jana ; Špolcová, Andrea ; Matyšková, Resha ; Blechová, Miroslava ; Veselá, Iva ; Železná, Blanka ; Maletínská, Lenka
We report specific binding of 125I-PrRP31 to the following cell lines: GH3 cells (rat – somatotrophs), AtT20 cells (mouse – adenocorticotrophs) and RC-4B/C cells (rat- somatotrophs, lactrophs, adenocortitrophs and gonadotrophs). These results will serve as a basic knowledge for future structure-activity studie sof PrRP.
|
|
| |
|
| |
|
| |
guest ::
