title: Secretion of neuropeptide Y in human adipose tissue and its role in maintenance of adipose tissue mass.
abstract: NPY is an important central orexigenic hormone, but little is known about its peripheral actions in human adipose tissue (AT) or its potential paracrine effects. Our objective was to examine NPY's role in AT, specifically addressing NPY protein expression, the effect of NPY on adipokine secretion, and the influence of insulin and rosiglitazone (RSG) on adipocyte-derived NPY in vitro. Ex vivo human AT was obtained from women undergoing elective surgery [age: 42.7 +/- 1.5 yr (mean +/- SE), BMI: 26.2 +/- 0.7 kg/m(2); n = 38]. Western blot analysis was used to determine NPY protein expression in AT depots. Abdominal subcutaneous (AbSc) adipocytes were isolated and treated with recombinant (rh) NPY, insulin, and RSG. NPY and adipokine levels were measured by ELISA. Our results were that NPY was localized in human AT and adipocytes and confirmed by immunohistochemistry. Depot-specific NPY expression was noted as highest in AbSc AT (1.87 +/- 0.23 ODU) compared with omental (Om; 1.03 +/- 0.15 ODU, P = 0.029) or thigh AT (Th; 1.0 +/- 0.29 ODU, P = 0.035). Insulin increased NPY secretion (control: 0.22 +/- 0.024 ng/ml; 1 nM insulin: 0.26 +/- 0.05 ng/ml; 100 nM insulin: 0.29 +/- 0.04 ng/ml; 1,000 nM insulin: 0.3 +/- 0.04 ng/ml; P < 0.05, n = 13), but cotreatment of RSG (10 nM) with insulin (100 nM) had no effect on NPY secretion. Furthermore, adipocyte treatment with rh-NPY downregulated leptin secretion (control: 6.99 +/- 0.89 ng/ml; 1 nmol/l rh-NPY: 4.4 +/- 0.64 ng/ml; 10 nmol/l rh-NPY: 4.3 +/- 0.61 ng/ml, 100 nmol/l rh-NPY: 4.2 +/- 0.67 ng/ml; P < 0.05, n = 10) but had no effect on adiponectin or TNF-alpha secretion. We conclude that NPY is expressed and secreted by human adipocytes. NPY secretion is stimulated by insulin, but this increment was limited by cotreatment with RSG. NPY's antilipolytic action may promote an increase in adipocyte size in hyperinsulinemic conditions. Adipose-derived NPY mediates reduction of leptin secretion and may have implications for central feedback of adiposity signals.
authors.affiliation: Unit for Diabetes and Metabolism, Clinical Sciences Research Institute, Warwick Medical School, Coventry, UK.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kos
authors.forename: Alison L
authors.initials: AL
authors.lastname: Harte
authors.forename: Sean
authors.initials: S
authors.lastname: James
authors.forename: David R
authors.initials: DR
authors.lastname: Snead
authors.forename: Joseph P
authors.initials: JP
authors.lastname: O'Hare
authors.forename: Philip G
authors.initials: PG
authors.lastname: McTernan
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
mesh_terms: D017667:Adipocytes / Q000502:physiology; D000328:Adult; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000502:physiology; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D047495:PPAR gamma / Q000819:agonists* / Q000494:pharmacology; D000077154:Rosiglitazone; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology