Role of the lipid-derived satiety factor, oleoylethanolamide, in PWS

Prader-Willi Syndrome (PWS) is a complex genetic disorder characterized by an insatiable feeling of hunger and an irrepressible urge to overeat. If left uncontrolled, hunger and overeating can lead to morbid obesity, diabetes, cardiovascular disease and premature death. Why PWS causes hunger is an important question that must be answered in we want to discover effective therapies for this syndrome. A significant step toward the solution of this problem was the recent discovery that mice engineered to carry a genetic mutation present in PWS develop, like children with PWS, an abnormally high appetite. Using these mutant mice, called ‘SNORD116del’, researchers may be able to identify specific biological mechanisms responsible for excessive hunger and overeating in PWS.

Our body produces various chemical substances that curb hunger. One of them, called oleoylethanolamide (OEA), is unique in that is exclusively released by fatty foods and decreases appetite both profoundly and persistently. Using SNORD116del mice and blood samples from PWS patients, we will test the hypothesis that the hunger-reducing signal provided by OEA is missing in PWS. We will ask three specific questions: 1. Is OEA formation impaired in SNORD116del mice? 2. Does treatment with OEA reduce hunger in SNORD116del mice? 3. Are OEA levels in blood altered in PWS patients?

If successful, our experiments will achieve two important objectives: first, they will help us understand why PWS causes overeating and, second, they will support the clinical testing of OEA, a natural compound present in various edible plants, as a therapy to reduce hunger in PWS.

Research Outcomes:

Dysfunctional oleoylethanolamide signaling in a mouse model of Prader-Willi syndrome. Igarashi M, Narayanaswami V, Kimonis V, Galassetti PM, Oveisi F, Jung KM, Piomelli D.  Pharmacological Research. 2017 Mar;117:75-81. 

Funded Year:


Awarded to:

Daniele Piomelli, Ph.D.




University of California, Irvine

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