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Obesity and severe co-morbid metabolic disorders are rapidly increasing in current society. Certain drugs can strongly influence the weight of patients. For instance Olanzapine -an antipsychotic drug - induces remarkable weight gain, whereas the anti-epileptic drug Topiramate induces weight loss and attenuates Olanzapine induced weight gain.
In this project a variety of teams, with specializations ranging from the molecular to the behavioral level, have joined forces to uncover the mechanisms behind the weight altering side effects of these model compounds. The knowledge generated may be used to develop new therapeutic strategies to treat human obesity and its metabolic consequences, including insulin resistance, metabolic syndrome and type 2 diabetes.
A clinical study to evaluate several observations obtained by the consortium is ongoing. This will bridge results between in-vitro, animal and human research, thus emphasizing the translational character of the project. Overall the results are promising and may lead to the development of new treatments for obesity and related metabolic disorders. A patent application is currently being investigated.
Full project title: Investigation of drug-induced weight alterations to identify novel therapeutic strategies for the treatment of obesity, dyslipidemia and diabetes
Start date: November 2006
End date: November 2011
Goal: Uncover the mechanisms underlying the effects of drug-induced weight alterations to develop novel therapeutic strategies to treat human obesity.
Principal investigator: Elwin Verheij
Project size: 9 FTE's
Partners: Abbott, Danone Research, Leiden University Medical Center, Netherlands Institute for Neurosciences, PRA International, TNO, University Medical Center Groningen
Obesity is a form of extreme overweight. Overweight is commonly assessed by the body mass index (BMI), which is expressed in kilograms per square meter. Healthy people have a BMI between 18.5 and 25, while in case of obesity the BMI is above 30. Due to this extreme overweight obese people have increased likelihood of developing serious illnesses such as heart disease, diabetes, cancer, and osteoarthritis. In general they are twice as likely to die prematurely compared to an average-weight person. Obesity is taking the form of an epidemic and not only affects industrialized countries but also poorer countries. Globally there are at least 300 million obese people. It is especially worrisome that there is an increased incidence in child obesity.
In general the cause of this epidemic is eating and exercise patterns. There is an increased consumption of energy-dense but nutrient-poor food. Furthermore there has been a serious reduction in physical activity over the last few decades, especially among children. As such obesity rates have risen more than three-fold since 1980 in industrialized countries such as the US and Europe, but also in China, the Middle East, Australasia and the Pacific Islands.
Claudia Coomans (project T2-105)
Elodie Girault (project T2-105)
The role of hypothalamic pathways in the metabolic side effects of Olanzapine