生物谷報道：最近,，喬治敦大學醫(yī)學中心的研究人員用簡單的，無毒性的化學注射劑來增加和轉移實驗室動物身體上的目標區(qū)域的脂肪,。這個在7月1日刊登在《自然藥物》上的發(fā)現,，可以極大改革人類的美容整形和重新整形外科手術和伴隨著人類肥胖而來的疾病的治療,。
    在報告中,，喬治敦研究人員描述了一個他們發(fā)現的壓力可以促進體重增加的機制,，該機制包括兩個參與者——一個神經傳遞素（神經肽Y，或NPY）和一個受體（神經肽Y2受體,，或Y2R）,，它在脂肪組織中以兩種類型的細胞活動：血管內皮細胞和脂肪細胞自身。為了選擇性地增加他們測試中的老鼠的脂肪,，研究人員把NPY打在一個特定的區(qū)域,。研究人員發(fā)現在壓力過程中NPY和Y2R都受到刺激，導致出現蘋果狀的肥胖和代謝綜合癥,。盡管如此,，體重增加和代謝綜合癥都是由Y2R阻滯劑阻止變?yōu)楦共恐镜摹?br />     這項發(fā)現為脂肪的重新塑造提供了可能性，,；并且已經得到了動物實驗結果的支持,。這些發(fā)現可能最終能夠控制代謝綜合癥，因為阻斷Y2R可能對人類起同樣的作用,，但需要更多的研究來證明它,。

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.

原文出處：
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

作者簡介：

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.