DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2009-04, Vol.11 (4), p.285-292
• Main Authors: Kos, K, Baker, A.R, Jernas, M, Harte, A.L, Clapham, J.C, O'Hare, J.P, Carlsson, L, Kumar, S, McTernan, P.G
• Format: Article
• Language: English
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; adipose tissue; Adult; Cells, Cultured; Dipeptidyl Peptidase 4 - metabolism; Dipeptidyl Peptidase 4 - physiology; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; DPP-IV; DPP-IV inhibitors; Female; Glycerol - metabolism; human metabolism; Humans; Lipolysis - drug effects; metabolic syndrome; Middle Aged; Neuropeptide Y - pharmacology; NPY; obesity; Obesity - metabolism; Obesity - pathology; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction - methods; Subcutaneous Fat, Abdominal - drug effects; Subcutaneous Fat, Abdominal - metabolism; Subcutaneous Fat, Abdominal - pathology
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2008.00909.x

Dipeptidyl peptidase IV (DPP-IV) inactivates the incretin hormone glucagon-like peptide. It can also affect the orexigenic hormone neuropeptide Y (NPY₁₋₃₆) which is truncated by DPP-IV to NPY₃₋₃₆, as a consequence NPY's affinity changes from receptor Y1, which mediates the antilipolytic function of NPY, to other NPY receptors. Little is known whether DPP-IV inhibitors for the treatment of type 2 diabetic (T2DM) patients could influence these pathways. To investigate the in vitro effects of NPY with DPP-IV inhibition in isolated abdominal subcutaneous (AbdSc) adipocytes on fat metabolism, and assessment of NPY receptor and DPP-IV expression in adipose tissue (AT). Ex vivo human AT was taken from women undergoing elective surgery (body mass index: 27.5 (mean ± s.d.) ± 5 kg/m², age: 43.7 ± 10 years, n = 36). Isolated AbdSc adipocytes were treated with human recombinant (rh)NPY (1-100 nM) with and without DPP-IV inhibitor (1 M); glycerol release and tissue distribution of DPP-IV, Y1 and Y5 messenger RNA (mRNA) were measured and compared between lean and obese subjects. rhNPY reduced glycerol release, an effect that was further enhanced by co-incubation with a DPP-IV inhibitor [control: 224 (mean ± s.e.) ± 37 μmol/l; NPY, 100 nM: 161 ± 27 μmol/l**; NPY 100 nM/DPP-IV inhibitor, 1 M: 127 ± 14 μmol/l**; **p < 0.01, n = 14]. DPP-IV was expressed in AbdSc AT and omental AT with relative DPP-IV mRNA expression lower in AbdSc AT taken from obese [77 ± 6 signal units (SU)] vs. lean subjects (186 ± 29 SU*, n = 10). Y1 was predominantly expressed in fat and present in all fat depots but higher in obese subjects, particularly the AbdSc AT-depot (obese: 1944 ± 111 SU vs. lean: 711 ± 112 SU**, n = 10). NPY appears to be regulated by AT-derived DPP-IV. DPP-IV inhibitors augment the antilipolytic effect of NPY in AT. Further studies are required to show whether this explains the lack of weight loss in T2DM patients treated with DPP-IV inhibitors.