Endocrine Abstracts

We have previously shown that the orexigenic hormone NPY is secreted by human adipocytes. The orexigenic hormone NPY(1–36) is truncated by the dipeptidyl-inhibitor IV (DPP-IV) to NPY(3–36) as consequence its affinity changes from receptor Y1 to Y4 and 5. The aim was to investigate whether DPP-IV is expressed in adipose tissue (AT) where it could modulate adipose tissue growth through modulation of NPY activity. This is relevant in light of DPP-IV inhibitors utilised as therapeutic agents and their use for treatment in Type 2 diabetes. For this purpose ex vivo human abdominal AT was taken from women undergoing elective surgery (BMI: 27.5(mean±S.D.)±5 kg/m², Age: 43.7±10 yrs, n=18). Isolated AbdSc adipocytes were treated with 1–100 nM rhNPY with and without DPP-IV inhibitors; a glycerol release assay was used as an index of lipolysis and DPP-IV mRNA expression assessed in AbdScAT. Treatment with NPY reduced glycerol release which was further blunted by co-incubation with DPP-IV inhibitors (baseline 234(mean±S.E.)±23 μmol/l, NPY100: 187±30μmol/l*; NPY100 with DPP-IV: 121±14 μmol/l**, *P<0.01, **P<0.01, n=8). Relative DPP-IV mRNA expression was reduced in AbScAT taken from obese subjects versus lean subjects (obese: 77±6 SU versus lean: 186±29 SU*, n=10).

In conclusion, paracrine effects of NPY may be modulated by AT-derived DPP-IV. Thus DPP-IV inhibitors may have little effect on tissue mass regulation in the obese where endogenous DPP-IV from AT is reduced, but may enhance fat accumulation in the lean through enhanced antilipolytic effects of NPY, which requires further study.