Projects
Drug-induced weight alterations
The overall goal of the project is to uncover the mechanisms underlying the side effects of drug-induced weight alterations (DIWA) to develop novel therapeutic strategies to treat human obesity. Olanzapine, an antipsychotic drug, induces weight gain, whereas the anti-epileptic drug Topiramate induces weight loss. These two drugs are used by the different teams to validate models, for example cell cultures, and techniques (mitochondria isolation, phosphoprotein analysis, proteomics, metabolomics) to identify candidate targets and novel therapeutic strategies for obesity. Experimental conditions to
reproduce human findings have not been fully established even though several experimental conditions (diet, mode of drug administration, treatment duration, etc.) have been used. Studies are ongoing to investigate central as well as peripheral targets. A short-term Topiramate treatment in obese insulino-resistant women has not demonstrated an improvement of insulin secretion, indicating that the observed beneficial effects after long-term treatment are probably mediated by weight loss.
Partners: Abbott, Danone Research, Leiden University Medical Center, Netherlands Institute for Neurosciences, PRA International, TNO, University Medical Center Groningen, the University Medical Center Utrecht and University of Groningen.
Full project title: Investigation of drug-induced weight alterations to identify novel therapeutic strategies for the treatment of obesity, dyslipidemia and diabetes