Endocrine Abstracts (2006) 11 P238

The depot specific expression of NPY in human adipose tissue and its upregulation under hyperinsulinaemic conditions in isolated human adipocytes

K Kos, AL Harte, P Gupta, P O’Hare, PG McTernan & S Kumar

Unit for Diabetes and Metabolism, Warwick Medical School, University of Warwick, Coventry, United Kingdom.

Neuropeptide Y (NPY) is a centrally expressed peptide with potent orexigenic properties, released post-prandially to stimulate appetite, regulated by insulin and altered by obesity. NPY is expressed in adipose tissue which suggests it may have a potential effect on altering appetite control in obesity. To date no study has investigated NPY and its regulation in human adipose tissue. Therefore, the aims of this study were to 1) determine the depot-specific expression in abdominal and gluteo-femoral fat 2) identify the adipocyte as a source of NPY in adipose tissue and 3) examine whether in vitro NPY secretion is stimulated by hyperinsulinaemic conditions. For this study, human adipose tissue was isolated from patients undergoing elective surgery (age±S.D.: 42.7±1.5 yr; BMI±S.D.: 26.2 Kg/m2±0.7; n=38), with local ethics approval. Western blot analysis was then used to determine depot specific NPY expression. Furthermore, isolated human abdominal subcutaneous (AbdSc) adipocytes were treated with insulin (1–1000 nM) for 48 hours and NPY levels in the conditioned media measured via ELISA. The ex vivo studies demonstrated that NPY protein expression in AbdSc ((AbdSc) n=20) was approximately 2 fold higher than both omental ((Om) n=8) and thigh (n=7); (AbdSc: 1.87±0.23, Om: 1.03±0.15, thigh: 1.0±0.29, P=0.029 and P=0.035, respectively). Western blotting also determined the presence of NPY protein within isolated AbdSc adipocytes, which was confirmed by immunohistochemical analysis. Analysis of NPY secretion (n=14) identified that insulin significantly increased NPY secretion (P<0.05). In summary, our present findings show that NPY is differentially expressed in human adipose tissue, with AbdSc demonstrating the highest levels. Further we have shown that NPY is secreted by isolated adipocytes and stimulated by insulin. In conclusion, NPY is expressed and secreted in human adipose tissue. Therefore increased NPY secretion from adipocytes, due to elevated insulin concentration, may contribute to the link between hyperinsulinaemia and continuing weight gain.

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