Neuropeptide Y is produced in visceral adipose tissue and promotes proliferation of adipocyte precursor cells via the Y1 receptor
Neuropeptide Y is produced in visceral adipose tissue and promotes proliferation of adipocyte precursor cells via the Y1 receptor
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DOI：
10.1096/fj.07-100735
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发表时间：
2008-07-01
期刊：
影响因子：
4.8
通讯作者：
Cao, Xiang
中科院分区：
文献类型：
--
作者：
Yang, Kaiping;Guan, Haiyan;Cao, Xiang
神经肽Y （NPY）是在中枢和周围神经系统的神经组织中合成的，除了调节食欲和能量稳态外，还具有许多重要的功能。在这里，我们发现了一个新的NPY生物合成位点和NPY在促进脂肪细胞前体细胞增殖中的作用。我们发现NPY mRNA不仅在内脏脂肪组织（VAT）中表达，而且在我们的早期内脏脂肪增加的程序化大鼠模型中，其水平上调了6倍。这伴随着NPY蛋白的平行上升，表明VAT是NPY生物合成的一个新的外周位点。此外，肥胖Zucker大鼠的VAT中NPY mRNA的表达也升高了2倍。重要的是，NPY在体外刺激原代大鼠前脂肪细胞和3T3-L1前脂肪细胞的增殖。这种有丝分裂效应似乎是由Y1受体介导的，并涉及细胞外相关激酶1/2的激活。此外，胰岛素和糖皮质激素上调了瘦型而非肥胖型Zucker大鼠的VAT NPY表达。综上所述，这些结果表明，VAT中NPY的局部表达增强可能是内脏脂肪增加的分子机制的共同特征。
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.