SD rat fed with a HF diet showed different susceptibility to obesity, and up-regulated hypothalamic NPY and Y1, Y2, Y5 receptor gene expressions were closely associated with being predisposed to obesity and overeating of DIO rats.
NPY deficiency attenuates the obesity syndrome of mice deficient for leptin (ob/ob), but these effects are not mediated by NPY signaling through the Y5R because Y5R-null ob/ob mice are equally obese.
Our data support the idea that the Y5 receptor is the postulated 'feeding' receptor, and may provide a new method for the study and treatment of obesity and eating disorders.