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Effects of ghrelin and its novel endogenous antagonist LEAP2 and their role in obesity
Tureckiová, Theodora ; Maletínská, Lenka (advisor) ; Selicharová, Irena (referee)
Obesity is a very dangerous metabolic disease, caused by the development of resistance to the anorexigenic (food intake reducing) hormone leptin, with an ever-increasing prevalence. Recently, both anorexigenic peptides and orexigenic (food intake increasing) peptide antagonists have emerged as candidates for the development of anti-obesity treatment. An example of such a peptide is the newly discovered endogenous ghrelin antagonist known as liver enriched antimicrobial peptide 2 (LEAP2). The uniqueness of the relationship between ghrelin and LEAP2 lies in the unusual occurrence of agonists and antagonists of the same receptor within the same organism. This receptor, known as growth hormone secretagogue receptor 1a (GHSR1a), is, among other roles, responsible for increased food intake and weight gain. Natural ghrelin and LEAP2 analogues, specifically non-lipidized LEAP2(1-14) fragment and lipidized (palmitoylated) palm-LEAP2(1-14) were used for studying their properties. The aim of this study was to demonstrate binding properties of LEAP2 analogues to the GHSR1a and to compare the effect of the lipidized analogue versus the non- lipidized one in vitro. Effects of the lipidated analogue were further investigated in vivo. Results of in vitro experiments demonstrated the binding of both LEAP2 analogues...
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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.
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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.
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