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DPP‐IV inhibition enhances the antilipolytic action of NPY in human adipose tissue
Author(s) -
Kos K.,
Baker A. R.,
Jernas M.,
Harte A. L.,
Clapham J. C.,
O’Hare J. P.,
Carlsson L.,
Kumar S.,
McTernan P. G.
Publication year - 2009
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2008.00909.x
Subject(s) - medicine , endocrinology , neuropeptide y receptor , adipose tissue , orexigenic , receptor , chemistry , dipeptidyl peptidase , context (archaeology) , ex vivo , biology , neuropeptide , in vitro , enzyme , biochemistry , paleontology
Context: Dipeptidyl peptidase IV (DPP‐IV) inactivates the incretin hormone glucagon‐like peptide. It can also affect the orexigenic hormone neuropeptide Y (NPY 1–36 ) which is truncated by DPP‐IV to NPY 3–36 , 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. Aims: 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). Methods: Ex vivo human AT was taken from women undergoing elective surgery (body mass index: 27.5 (mean ± s.d.) ± 5 kg/m 2 , 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. Results and conclusion: 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.