Atrial natriuretic peptide (ANP) is a 28-amino acid polypeptide that. is primarily secreted by the heart. ANP is believed to be a hormone that. regulates cardiovascular dynamics and renal functions: however, studies conducted in the past few decades revealed that ANP is also a potent lipolytic agent in human adipocyt.es that. functions through the cGMP-dependent pathway. In this study. we separated human adipocyt.es within the same I-at depot into small and large fractions using their floating properties and nylon filters of different pore sizes. Real-time PCR revealed that large adipocytes expressed higher mRNA levels of natriuretic peptide receptor (NPR)-A and hormone sensitive lipase. and binding studies showed that large adipocytes expressed more NPR-A on the membrane than small adipocytes. This finding was confirmed by the increase in the amount of glycerol that was released from adipocytes as the cell size increased. Taken together. these results clearly suggest. that adipocyte size is an important determinant of ANP-stimulated lipolysis. Copyright (C) 2008 European Peptide Society and John Wiley & Sons. Ltd.