Periodic Report Summary - GIPIO (Gastro-intestinal Peptides in Obesity)
Project context and objectives:
Obesity is one of the fastest growing health problems in the western world and many developing countries. In the United States, obesity as a cause of preventable mortality (365 000 deaths in 2000) will soon overtake tobacco (435 000 deaths) and already has overtaken alcohol consumption (85 000 deaths), infectious diseases (75 000) and motor vehicle crashes (43 000). More importantly, it is also a problem in children and adolescents, and one of the major future health problems. We hypothesise that the reduction of hormones / signals, released or blocked after food intake, significantly contributes to the feed-back upon food intake, and subsequently to the onset in obesity. Accordingly, the focus of this project is to better understand the contribution of gastro-intestinal peptides to the onset of obesity. It is aimed to identify the most relevant hormones or combinations of hormones, and subsequently to develop anti-obesity drugs that are based on endogenous hormone agonists or antagonists.
Project results:
The project work started in October 2008. The first scientific report has been submitted in May 2010. The major tasks of the consortium during the second phase of the project (month 19-36 April 2010 to September 2011) has been:
- synthesis and analysis of peptide hormones;
- study of in vivo functions of native hormones in animals and man;
- modification and optimisation of native peptide hormones;
- development of promising anti-obesity compounds based on inverse agonist, agonist and antagonist concepts;
- analysis of the metabolic stability and biodistribution of modified peptides.
Potential impact:
Specific scientific impact: In the second phase, we made critical steps towards understanding structural conformations of peptide hormones and established advanced production methods for these compounds. We optimised native hormones to make them more stable and increased their bioavailability. Furthermore, we developed bioassays to analyse activity in different tissues and under different conditions in animals and man. Important steps were standardisation tasks to assure comparability in the testing conditions of novel compounds. In the next and last period, the elucidation of the cellular and molecular pathophysiological mechanisms involved in obesity and its correlation with nutrition-dependent hormone release will be investigated.
Health impact: Although obesity and most cases of type-2 diabetes could in principle be cured or prevented by lifestyle changes in respect of physical activity and healthy food intake, this clearly does not work in reality as the obesity and diabetes incidence appears to be increasing almost exponentially. In respect of pharmaceuticals for weight control, there are only a few drugs available and these are characterised by low efficacy (approximately 5 % weight reduction) and poor tolerability and / or side effects. The only notably efficacious treatment of obesity is bariatric surgery, which also is very effective against type-2 diabetes. The focus of the present project is to identify the most relevant hormones and combinations of hormones, understand their mode of release and activity, and to use this knowledge and these peptide hormones as the basis for the development of novel anti-obesity drugs in the form of agonists, inverse-agonists or antagonists - providing the benefits of bariatric surgery without the risks of such invasive procedures.
Project website: http://www.gipio.eu
Obesity is one of the fastest growing health problems in the western world and many developing countries. In the United States, obesity as a cause of preventable mortality (365 000 deaths in 2000) will soon overtake tobacco (435 000 deaths) and already has overtaken alcohol consumption (85 000 deaths), infectious diseases (75 000) and motor vehicle crashes (43 000). More importantly, it is also a problem in children and adolescents, and one of the major future health problems. We hypothesise that the reduction of hormones / signals, released or blocked after food intake, significantly contributes to the feed-back upon food intake, and subsequently to the onset in obesity. Accordingly, the focus of this project is to better understand the contribution of gastro-intestinal peptides to the onset of obesity. It is aimed to identify the most relevant hormones or combinations of hormones, and subsequently to develop anti-obesity drugs that are based on endogenous hormone agonists or antagonists.
Project results:
The project work started in October 2008. The first scientific report has been submitted in May 2010. The major tasks of the consortium during the second phase of the project (month 19-36 April 2010 to September 2011) has been:
- synthesis and analysis of peptide hormones;
- study of in vivo functions of native hormones in animals and man;
- modification and optimisation of native peptide hormones;
- development of promising anti-obesity compounds based on inverse agonist, agonist and antagonist concepts;
- analysis of the metabolic stability and biodistribution of modified peptides.
Potential impact:
Specific scientific impact: In the second phase, we made critical steps towards understanding structural conformations of peptide hormones and established advanced production methods for these compounds. We optimised native hormones to make them more stable and increased their bioavailability. Furthermore, we developed bioassays to analyse activity in different tissues and under different conditions in animals and man. Important steps were standardisation tasks to assure comparability in the testing conditions of novel compounds. In the next and last period, the elucidation of the cellular and molecular pathophysiological mechanisms involved in obesity and its correlation with nutrition-dependent hormone release will be investigated.
Health impact: Although obesity and most cases of type-2 diabetes could in principle be cured or prevented by lifestyle changes in respect of physical activity and healthy food intake, this clearly does not work in reality as the obesity and diabetes incidence appears to be increasing almost exponentially. In respect of pharmaceuticals for weight control, there are only a few drugs available and these are characterised by low efficacy (approximately 5 % weight reduction) and poor tolerability and / or side effects. The only notably efficacious treatment of obesity is bariatric surgery, which also is very effective against type-2 diabetes. The focus of the present project is to identify the most relevant hormones and combinations of hormones, understand their mode of release and activity, and to use this knowledge and these peptide hormones as the basis for the development of novel anti-obesity drugs in the form of agonists, inverse-agonists or antagonists - providing the benefits of bariatric surgery without the risks of such invasive procedures.
Project website: http://www.gipio.eu