Nutritional aspects of PWS and childhood obesity: a metabolomics approach
Funding Summary
Lay Abstract
In Prader-Willi syndrome (PWS) the progression from poor appetite and failure-to-thrive (FTT) to obesity and voracious appetite is complex and takes several years. We have recently shown that there are 6 distinct post-natal nutritional phases in PWS. By looking at the end products of cellular processes in individuals with PWS before and after the onset of obesity and hyperphagia, we hope to understand the cellular mechanism(s) and biochemistry governing this shift.
We will characterize the unique chemical fingerprint (metabolites*) of individuals with PWS in the 6 different nutritional phases. These metabolites include amino acids and products of amino acid and fatty acid metabolism. Fasting plasma samples from individuals with PWS and non-PWS individuals with earlyonset morbid obesity (EMO) will also be compared. Samples from age-matched siblings with normal weight will be used as controls. A standard statistical approach will be used for biomarker identification under the supervision of a professional statistician who will also assist in the project design. We are fortunate to have world class core facility at our institution to assist us in these analyses.
In the long term the utility of knowing the mechanism(s) involved in the transition to each phase will give scientists incredible insight into the pathophysiology of obesity in PWS and therefore lead to rationale treatment strategies. In addition insights into the causes of obesity in PWS will undoubtedly make valuable contributions into other causes of obesity in the general population. The development of biomarkers that can predict pre-symptomatically the development of obesity later.