生物谷报道：最近，乔治敦大学医学中心的研究人员用简单的，无毒性的化学注射剂来增加和转移实验室动物身体上的目标区域的脂肪。这个在7月1日刊登在《自然药物》上的发现，可以极大改革人类的美容整形和重新整形外科手术和伴随着人类肥胖而来的疾病的治疗。
在报告中，乔治敦研究人员描述了一个他们发现的压力可以促进体重增加的机制，该机制包括两个参与者——一个神经传递素（神经肽Y，或NPY）和一个受体（神经肽Y2受体，或Y2R），它在脂肪组织中以两种类型的细胞活动：血管内皮细胞和脂肪细胞自身。为了选择性地增加他们测试中的老鼠的脂肪，研究人员把NPY打在一个特定的区域。研究人员发现在压力过程中NPY和Y2R都受到刺激，导致出现苹果状的肥胖和代谢综合症。尽管如此，体重增加和代谢综合症都是由Y2R阻滞剂阻止变为腹部脂肪的。
这项发现为脂肪的重新塑造提供了可能性，；并且已经得到了动物实验结果的支持。这些发现可能最终能够控制代谢综合症，因为阻断Y2R可能对人类起同样的作用，但需要更多的研究来证明它。
Figure 1 - Stress, in the presence of an HFS diet, causes the upregulation of plasma NPY and fat Npy, Npy2r and Dpp4 expression, increasing visceral fat growth
(a) Levels of NPY-IR in platelet-poor plasma (PPP) and platelet-rich plasma (PRP) from 129X1/SvJ mice under conditions of a HFS diet, cold, cold + an HFS diet, and aggressor (Aggr) + an HFS diet compared to non-stressed standard chow-fed control (CTL). (b) Changes in visceral fat measured by 3D-MRI volume reconstruction imaging of fat in mice on HFS diet, cold + HFS, and Aggr + HFS, compared to non-stressed mice on standard chow diet (CTR). (c) Representative images of fat, assessed by 3D-MRI, with whole mice at left (rostral end up) and cross-sections at right. Scale bar, 1 cm. S, spine; K, kidney; I, intestines. (d) Npy, Dpp4 and Npy2r mRNA levels in subcutaneous abdominal fat of HFS and cold stress treated mice as compared to untreated control mice (quantitative real-time PCR). (e,f) Immunohistochemistry of Npy (e) and Npy2r (f) localized to vessels and adipocytes in subcutaneous abdominal fat in mice. Scale bars, 20 m. The results represent average values s.e.m. of n = 6 mice. *P < 0.05, **P < 0.01 by one-way ANOVA with Bonferroni's multiple t-test. ND, not detected.
原文出处：
Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome
Lydia E Kuo, Joanna B Kitlinska, Jason U Tilan, Lijun Li, Stephen B Baker, Michael D Johnson, Edward W Lee, Mary Susan Burnett, Stanley T Fricke, Richard Kvetnansky, Herbert Herzog & Zofia Zukowska
Published online: 01 July 2007; | doi:10.1038/nm1611
Abstract | Full Text | PDF (536 KB) | Supplementary information
作者简介：
Zofia Zukowska, M.D., Ph.D.
RESEARCH INTERESTS
We focus on Neuropeptide Y (NPY), a major neurotransmitter in the central and peripheral nervous system, hormone and immunomodulator. NPY has pleiotropic activities ranging from stimulating appetite, obesity and anxiolysis, modulation of endocrine functions such as secretion of insulin and pituitary-adrenal hormones, to cardiovascular regulation such as vasoconstriction and vascular remodeling. These activities are mediated by activation of multiple Gi/o-coupled receptors, designated Y1-Y5.
Since the discovery of NPY in 1982 (Tatemoto and Mutt), our lab has pioneered many of the studies dealing primarily with peptide?s role in cardiovascular physiology and pathophysiology. We have found that NPY is a mediator of severe and/or prolonged stress and is responsible for slow-onset but long-lasting vasoconstriction via Y1 receptors. Males release more NPY during stress and are more sensitive to its hypertensive effects due to testosterone-dependent regulation of the NPY gene. In the last couple of years, the focus of the lab has moved towards more chronic effects of NPY on the cardiovascular system since we discovered its ability to stimulate vascular smooth muscle growth.
Using combination of integrative physiology, cellular and molecular biology, we have established that NPY is extremely potent (active at sub-picomolar concentrations) and powerful (similarly to many known growth factors) vascular mitogenic and angiogenic factor. More recent studies indicate that NPY is a sympathetic trophic factor regulating vascular remodeling in hypertension, atherosclerosis and re-stenosis, and a mediator of neurogenic angiogenesis in ischemic cardiovascular diseases, cancer, aging and obesity. A major part of the current studies is aimed at establishing which of the multiple NPY receptors are responsible for specific functions and what cellular mechanisms mediate NPY?s growth promoting effects. Another part of this research is to determine the interaction of NPY with the adrenergic system, for which it serves as a co-transmitter, and other vascular mitogenic and angiogenesis factors, such as VEGF.
Finally, we try to link animal findings with the human data. Recently, several epidemiological studies carried out in Europe supported our experimental results implicating NPY as a risk factor for atherosclerosis. A common single nucleotide polymorphism was found in the NPY signal peptide gene (Karvonen et al, 2000), which apparently makes the peptide more releasable in response to stressors (Kallio et al, 2001), and is highly correlated with increased plasma lipid levels and accelerated atherosclerosis (Karvonen et al. 2001). Whether or not NPY indeed exerts deleterious effects on the cardiovascular system - as a risk factor for atherosclerosis and stress-induced vasoconstrictor - or is beneficial - by augmenting ischemic angiogenesis - appear to depend on the type of receptors expressed in the tissues? And what are the factors which regulate NPY receptors?is the next question, which we are addressing?
Other links of interest:
http://myprofile.cos.com/zukowska
http://zukowska.tekdeezine.com/For publications, go to PubMed at the following link:
http://www.ncbi.nlm.nih.gov/entrez/ and use "Zukowska" and "Zukowska-Grojec" to find a complete listing.
