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FASEB J. 2008 Jul;22(7):2452-64. doi: 10.1096/fj.07-100735. Epub 2008 Mar 6.

Neuropeptide Y is produced in visceral adipose tissue and promotes proliferation of adipocyte precursor cells via the Y1 receptor.

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Children's Health Research Institute, Rm. A5-132, Victoria Research Laboratories,Westminster Campus, 800 Commissioners Rd. East, London, Ontario, Canada N6A 4G5.


Neuropeptide Y (NPY) is synthesized in neural tissue of the central and peripheral nervous systems and has a number of important functions besides regulating appetite and energy homeostasis. Here we identify a novel site of NPY biosynthesis and a role for NPY in promoting proliferation of adipocyte precursor cells. We show that NPY mRNA is not only expressed in visceral adipose tissue (VAT) but that its levels are up-regulated 6-fold in our early-life programmed rat model of increased visceral adiposity. This is accompanied by a parallel rise in NPY protein, demonstrating that VAT is a novel peripheral site of NPY biosynthesis. Furthermore, NPY mRNA expression is also elevated >2-fold in VAT of obese Zucker rats. Importantly, NPY stimulates proliferation of primary rat preadipocytes as well as 3T3-L1 preadipocytes in vitro. This mitogenic effect appears to be mediated by the Y1 receptor and involves the activation of extracellular related kinase 1/2. In addition, insulin and glucocorticoid up-regulate VAT NPY expression in lean but not obese Zucker rats. Taken together, these results suggest that an enhanced local expression of NPY within VAT may be a common feature of and contribute to the molecular mechanisms underlying increased visceral adiposity.

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