Characterization of NPY receptors controlling lipolysis and leptin secretion in human adipocytes

In order to characterize neuropeptide Y (NPY) receptors present in human adipocytes, we used selective ligands together with specific molecular probes able to recognize the different NPY receptor subtypes. RT‐PCR experiments revealed the presence of Y1 receptor transcripts with Y4 and Y5 and absence of Y2 signals. Binding studies, using selective radioiodinated ligands, detected a high number (B max=497±124 fmol/mg protein) of a high affinity binding site only with [125I]peptide YY (PYY) and [125I](Leu31,Pro34)PYY. These sites exhibited a typical Y1 profile as indicated by the rank order of affinity of NPY analogs and the high affinity of two selective NPY receptor antagonists, SR120819A and BIBP3226. In [35S]GTPγS binding experiments, PYY activation was totally inhibited by SR120819A and BIBP3226. Both compounds antagonized, with similar efficiency, the antilipolytic effect exerted by NPY in isolated adipocytes. Finally, PYY and Y1 ligands enhanced adipocyte leptin secretion, an effect totally prevented by SR120819A. Thus, highly expressed in human adipocytes, the Y1 receptor sustains the strong antilipolytic effect of NPY and exerts a positive action on leptin secretion.