Increased insulin concentrations and glucose storage in neuropeptide YY1 receptor-deficient mice

Mice lacking NPY Y1 receptors develop obesity without hyperphagia indicatin g increased energy storage and/or decreased energy expenditure. Then, we in vestigated glucose utilization in these animals at the onset of obesity. Fa sted NPY YI knockouts showed hyperinsulinemia associated with increased who le body and adipose tissue glucose utilization and glycogen synthesis but n ormal glycolysis. Since leptin modulates NPY actions, we studied whether th e lack of NPY Y1 receptor affected leptin-mediated regulation of glucose me tabolism. Leptin infusion normalized hyperinsulinemia and glucose turnover. These results suggest a possible mechanism for the development of obesity without hyperphagia via dysfunction in regulatory loops involving NPY, lept in and insulin. (C) 2001 Elsevier Science Inc. All rights reserved.