醛固酮对大鼠血浆神经肽Y的影响

目的 :探讨醛固酮 （Ald）诱导心肌肥大的大鼠模型中 ,血浆神经肽 Y（NPY）含量的变化。方法 :健康雄性 Wis-tar大鼠 2 1只 ,随机分为 3组 :1正常对照组 ;2心肌肥大组 :皮下注射 Ald18μg/d× 14 d;3螺内酯组 :皮下注射Ald18μg/d、螺内酯 2 0 m g· kg- 1· d- 1灌胃连续 14 d。测量尾动脉压 ,取心脏测量左心室质量 /体质量 （L VW/BW）比值 ,用放免方法测定血浆 NPY、血管紧张素 （Ang ）、Ald含量。结果 :心肌肥大组较正常 L VW/BW升高 ,NPY和 Ang 下降 ,Ald增加 ;螺内酯组较心肌肥大组 L VW/BW降低 ,NPY、Ang 和 Ald增加。结论 :外源性 Ald通过与受体结合可负性调控 NPY的分泌。     

Induction and reversibility of an obesity syndrome by intracerebroventricular neuropeptide Y administration to normal rats

Summary Intracerebroventricular neuropeptide Y (NPY) administration to normal rats for 7 days produced a sustained, threefold increase in food intake, resulting in a body weight gain of more than 40 g. Basal plasma insulin and triglyceride levels were increased in NPY-treated compared to vehicle-infused rats by about four- and two-fold, respectively. The glucose utilization index of white adipose tissue, measured by the labelled 2-deoxy-d-glucose technique was four times higher in NPY-treated rats compared to controls. This change was accompanied by an increase in the insulin responsive glucose transporter protein (GLUT 4). In marked contrast, muscle glucose utilization was decreased in NPY-treated compared to vehicle-infused animals. This change was accompanied by an increase in triglyceride content. When NPY-treated rats were prevented from overeating, there was no decrease in muscle glucose uptake, nor was there an increase in muscle triglyceride content. This suggests that muscle insulin resistance of ad libitum-fed NPY-treated rats is due to a glucose-fatty acid (Randle) cycle. When intracerebro-ventricular NPY administration was stopped and rats kept without any treatment for 7 additional days, all the abnormalities brought about by the neuropeptide were normalized. A tonic central effect of NPY is therefore needed to elicit and maintain most of the hormonal and metabolic abnormalities observed in the present study. Such abnormalities are analogous to those seen in the dynamic phase of obesity syndromes in which high hypothalamic NPY levels have been reported.Abbreviations NPY Neuropeptide Y - icv intracerebroventricular - GLUT 4 glucose transporter 4     

Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression

Aims: Dietary fatty acid profile, independent of caloric percent of fat, is a major regulator of body adiposity. This study examined the effects of dietary fat amount and types on fat storage and hypothalamic gene expression in the mouse model of chronic diet‐induced obesity. Methods: The dietary interventions were in twofold: (1) the obesity was induced by a 13‐week obesogenic fat diet compared with a low‐fat (LF) diet, and (2) the reversibility was tested by using high n‐3 polyunsaturated fat (PUFA) and LF diets. Fifty‐four C57Bl/6 mice were fed a high‐fat (59% in kcal) diet for 13 weeks and then classified as diet‐induced obese (DIO) or diet‐resistant (DR) mice according to upper and lower tertiles of body weight gain. The DIO mice were then subdivided into three groups for a 6‐week secondary dietary intervention. Two of the groups were switched to either a high n‐3 PUFA (DIO‐n3) or a low‐fat (10% in kcal, DIO‐LF) diet, whereas the third (controls) and DR mice continued on the initial high‐fat diet. Food efficiency was calculated as weekly body weight gain per gram of food intake. Results: After switching the DIO mice to the n‐3 PUFA or LF diet, their body weights were reduced to the level of the DR and LF mice. The food efficiencies were, from the highest to lowest, in the order: DIO > LF > DR > DIO‐LF > DIO‐n3. Using quantitative in situ hybridization, we found that the DIO mice had higher levels of leptin receptor (LR, +290%, p < 0.005) and neuropeptide Y (NPY, +25%, p < 0.05) mRNA expression in the hypothalamic arcuate nucleus (Arc) than the DR mice, whereas the level of pro‐opiomelanocortin (POMC) mRNA expression was significantly reduced (?45%, p < 0.01). All effects that were essentially returned to DR levels by the change to the n‐3 PUFA diet and, with the exception of a failure to normalize Arc NPY mRNA levels, by the change to LF diet. Conclusions: Taken together, the present results show that both change in level and quality of dietary fat can potently alter hypothalamic neuropeptide expression and result in effective amelioration of diet‐induced obesity. Interestingly, the n‐3 PUFA diet when fed to already obese mice produced a pattern of hypothalamic gene expression similar to that in obesity resistant (DR) mice. It remains to be determined if the effects of n‐3 fatty acids on brain neuropeptide gene expression are direct or indirect.     

肝硬化患者检测血浆神经肽Y的临床意义

研究肝硬化患者血浆神经肽Y的变化及其临床意义。肝硬化患者 6 4例。男 40例 ,女 2 4例 ,平均年龄 45岁± 2 3岁。其中乙型肝炎性肝硬化 5 7例 ,丙型肝炎性肝硬化 2例 ,酒精性肝硬化 4例 ,心源性肝硬化 1例 ,伴消化道出血 2 0例 ,腹水 36例 ,肝性脑病 12例和肝肾综合症 4例。按肝功能分级Child分级 :A级 2 8例 ,B级 2 3例 ,C级 13例。采用RIA法检测空腹血浆NPY水平 ,并与 40例 (男 2 6例 ,女 14例 ,平均年龄 42岁± 2 0岁 )健康人作对照。肝硬化A级患者血浆NPY含量 (12 1 6± 2 8 9) pg/ml低于健康对照组 (142 3± 40 5 ) pg/ml(P <0 0 5 )。肝硬化B级 (6 3 4± 2 4 8) pg/ml,C级 (4 5 6± 2 1 7) pg/ml患者血清NPY含量显著低于健康对照组及肝硬化A级患者 (P <0 0 1)。肝硬化患者血浆NPY含量显著低下 ,并随肝功能损害程度加重而下降更多 ,提示NPY可能参与了肝损害的病理过程 ,并与肝功能分级有关。     

Genetic association studies of obesity in Africa: a systematic review

Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome‐wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies.     

环孢素A调控肾性高血压大鼠血浆神经肽Y的作用机制

目的:探讨一肾一夹肾性高血压大鼠模型中,血浆神经肽Y（NPY）含量变化调控机制。方法:健康雄性Wistar大鼠,随机分为3组。①假手术组;②高血压组:通过一肾一夹法复制肾性高血压大鼠;③环孢素A组:环孢素A（CsA）5mg·kg-1·d-1皮下注射;全部大鼠均在实验14d后,测量尾动脉压,取心脏测量左心室质量/体质量（LVW/BW）,用放免方法测定血浆NPY、血管紧张素Ⅱ（AⅡ）、醛固酮（Ald）含量。结果:高血压组较假手术组BP、LVW/BW升高,NPY下降,Ald增加;CsA组较高血压组LVW/BW降低,NPY增加,Ald无显著变化。结论:Ald对血浆NPY水平的负性调控,是通过CaN信号转导通路介导而发生的。     

老年单纯收缩期高血压患者血浆中神经肽Y浓度的变化

目的　观察老年单纯收缩期高血压 (ISH)患者血浆神经肽Y(NPY)浓度的变化 ,并探讨其临床意义。方法　采用放射免疫法测定 40例ISH患者血浆NPY浓度 ,其中 30例应用彩色多普勒超声心动图仪测定左室射血分数。结果　 (1)ISH患者NPY浓度较正常对照组明显升高 (P <0 .0 1)。且NPY的浓度与收缩压增高的幅度呈正相关。(2 )ISH患者血浆NPY浓度 1级最低 ,2级居中 ,3级最高 ,各级之间差异有显著性意义 (F =6 7.5 8,P <0 .0 1)。(3)血浆NPY浓度随心功能损害程度加重而上升 (F=5 9.6 8,P <0 .0 1)。结论　NPY可能参与高血压的发生和发展 ,并与病情有关。检测血浆NPY浓度可作为判断ISH患者病情的指标     

高血压病患者血浆神经肽Y水平改变的比较研究

目的　探讨高血压病患者血浆神经肽Y(neu ropeptideY ,NPY)、肾上腺素 (adrenaline)水平的改变及苯那普利、缬沙坦的干预影响。方法　采用同位素放射免疫分析法 ,对 80例高血压患者和 30例正常健康人进行血浆NPY、肾上腺素水平测定 ,高血压患者分成两组 ,分别给予苯那普利、缬沙坦治疗 4w ,测定服药后该指标的变化。结果　高血压患者血浆NPY含量为 (15 1 39± 2 5 32 )pg/ml明显高于正常对照组 (10 1± 10 4 )pg/ml,肾上腺素含量为 (10 3 12±16 2 5 )pg/ml明显高于正常对照组 70 4 5pg/ml ;药物治疗后血浆NPY、肾上腺素较治疗前明显下降 ;但两组药物干预比较无明显差异。结论　高血压患者血浆NPY、肾上腺素水平增高 ,存在神经内分泌的激活 ;应用血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂治疗后可使血浆NPY和肾上腺素水平下降 ,这可能是苯那普利和缬沙坦的降压机制之一。     

An immunohistochemical study of neuropeptide Y in the bovine pineal gland

Abstract: An immunohistochemical study of the bovine pineal gland was performed using rabbit polyclonal antibodies raised against neuropeptide Y (NPY) or against the C-terminal flanking peptide of proNPY (CPON). A large number of NPY/CPON-immunoreactive (IR) nerve fibers were demonstrated throughout bovine pineal gland. The IR-fibers were located in the capsule of the gland, usually piercing into the gland together with blood vessels. In the gland itself, the fibers wen also located intraparenchymally between the pinealocytes. Within the rostral and caudal areas of the pineal stalk, NPY-IR fibers were also observed, and these fibers could be followed not only into the gland bul also to the habenular and posterior commissures. The morphological localization of the NPY-IR nerve fibers in the bovine pineal gland indicate that the majority of fibers originate from the superior cervical ganglion. However, some fibers probably originate from the brain itself.     

Cloning and sequence analysis of the neuropeptide Y receptors Y5 and Y6 in the coelacanth Latimeria chalumnae

Two coelacanth species, Latimeria chalumnae and Latimeria menadoensis, the recently discovered second species, have a key evolutionary position at the divergence of bony fishes and tetrapods. Together with lungfishes, they are the only living species separating the species-rich tetrapods from the other major group of vertebrates, the ray-finned fishes. The coelacanth is therefore of great importance for comparisons of gene families that differ between these two groups, such as the neuropeptide Y (NPY) receptor family. In this work we have sequenced the full-length genes for two NPY receptors in Latimeria chalumnae. Phylogenetic analysis indicated that the two sequences are orthologs of the mammalian Y5 and Y6 receptors. The Y5 gene has been implicated in appetite stimulation in mammals but is absent from teleost fishes. The presence of the Y5 receptor in Latimeria together with phylogenetic analysis shows that Y5 existed before the separation of bony fishes and tetrapods. The Latimeria receptor has about 62% identity to tetrapod Y5 sequences and contains the extended third intracellular loop with several highly conserved motifs that may be involved in signal transduction. The Latimeria Y6 receptor has about 60% identity to tetrapod Y6 sequences. The functional role of Y6 is unclear as the gene is seemingly functional in some mammals but is non-functional in others. The Y6 receptor is also missing in teleost fishes. Our results confirm an early vertebrate origin for all NPY receptor subtypes presently found in mammals followed by differential gene loss in the different classes of vertebrates.     

Plasma chromogranin A + B,neuropeptide Y and catecholamines in pheochromocytoma patients

Abstract. Plasma levels of chromogranin A + B, neuropeptide Y and catecholamines were analysed before, during and after surgery in seven patients with pheochromocytoma. The aim of the study was to determine the diagnostic sensitivity of these plasma amines and peptides, and to investigate their peroperative fluctuations. Chromogranin A + B in plasma was increased preoperatively in all patients, showed no significant increase during surgery, and normalized postoperatively. Neuropeptide Y, which alone can induce hypertension, was present in high levels in plasma from three patients preoperatively, increased further in four patients during surgery, and was postoperatively low in all patients. Fractionated plasma catecholamines were increased in five patients before surgery, increased in all patients during tumour dissection, and normalized postoperatively. It may be concluded that plasma chromogranin A + B exhibited as high a sensitivity for pheochromocytoma as fractionated urinary catecholamines in the patients studied.     

肠癌患者血清巨噬细胞抑制因子-1、神经肽Y的表达与食欲减退的相关性

[目的]探讨肠癌患者血清巨噬细胞抑制因子-1(MIC-1)、神经肽Y(NPY)的表达及其与患者食欲减退的相关性.[方法]采用ELISA法测定34例晚期肠癌患者3个月前后血清MIC-1、NPY的表达,并进行食欲评分和体质指数计算.[结果]研究前34例患者MIC1、NPY水平分别为(947.55±82.83)、(118.59±8.55) pg/ml;随访3个月后有6例患者死亡,余28例患者MIC-1水平升高为(1195.09±122.32) pg/ml,NPY水平下降至(99.20±7.33)pg/ml;前、后比较均差异有统计学意义(P＜0.01).3个月后食欲评分及体质指数均较研究前下降;食欲评分及体质指数与血清MIC-1呈显著负相关,与NPY呈显著正相关(均P＜0.01).[结论]晚期肠癌患者血清MIC-1表达升高而NPY表达下降,两者与食欲评分及体质指数的下降密切相关,是导致晚期肠癌患者食欲减退和体质量下降的原因之一.     

原发性高血压患者血浆瘦素与神经肽Y浓度测定的意义

目的　研究原发性高血压患者神经肽Y与瘦素的相互关系。方法　采用放免分析法测定 2 6例健康对照者和原发性高血压 1级 4 2例、2级 4 6例及 3级 2 8例患者的空腹血浆瘦素 (LE)及神经肽Y (NPY)浓度。结果　血浆LE及NPY浓度均随血压的升高而升高 (F分别为 4 0 2和31 4 ,P均 <0 0 0 1) ,在正常对照组和高血压各组间均有显著性差异。相关分析表明 ,NPY和LE均与血压呈显著正相关 ,控制LE的影响后NPY仍与血压呈正相关 (P均 <0 0 5 ) ,而控制NPY的影响后LE与血压的相关性不再有显著性 (P >0 0 5 )。NPY浓度与LE浓度呈显著正相关 (R =0 5 5 9,P<0 0 0 0 1) ,同时控制性别、血压、血脂、BMI和HOMA IR的影响后两者仍呈显著正相关 (R =0 337,P <0 0 0 0 1)。结论　高血压患者存在瘦素抵抗 ,瘦素抵抗可能是高血压患者NPY升高的主要原因 ,而NPY的升高一方面可使血压升高 ,另一方面可能进一步加重瘦素抵抗。     

脑出血大鼠血浆神经肽Y及血清肌酸磷酸激酶MB型的变化

目的　观察实验性脑出血条件下血浆神经肽Y(NPY)及肌酸磷酸激酶MB型 (CK MB)含量的动态变化 ,以探讨脑心综合征的发生机制。方法　采用胶原酶和肝素联合注入尾状核方法建立大鼠脑出血模型 ,测定出血前、出血后 30min、6、12、2 4、4 8及 72h血浆NPY活性及血清CK MB变化。采用放射免疫法测定血浆NPY的变化 ,采用酶反应速率法测定血清CK MB的变化。结果　大鼠脑内血肿开始形成的 6h血浆NPY活性、血清CK MB均较术前水平及对照组显著升高 (P <0 .0 5 ) ,并以脑出血 2 4h血肿高峰期时最为显著 (P <0 .0 1) ,随后逐渐下降 ,72h仍高于术前水平及对照组 (P <0 .0 5 )。结论　脑出血时常伴有血清CK MB改变 ,外周NPY含量升高可能参与脑心综合征的发生发展。     

神经肽Y Y5受体基因反义寡核苷酸脑室给药对肥胖大鼠外周瘦素抵抗的影响

目的 探讨神经肽Y（NPY）Y5受体基因反义寡核苷酸脑室给药对饮食所致肥胖大鼠外周瘦素抵抗的影响。方法 （1）建立高营养饲料诱导的肥胖大鼠模型，侧脑室插管后注射NPY Y5受体基因反义、错义寡核苷酸及生理盐水，观察大鼠腹膜后脂肪湿重的变化；（2）采用ELISA双抗体夹心法测定血清瘦素含量、放免法测定血清胰岛素含量，RT－PCR技术检测脂肪组织中ob基因的表达水平，评价该疗法对肥胖大鼠外周瘦素抵抗的影响。结果 经NPY Y5受体基因反义寡核苷酸干预后，肥胖大鼠腹膜后脂肪湿重、血清胰岛素含量、血清瘦素含量、腹膜后脂肪组织ob基因mRNA表达水平均明显降低，降腹膜后脂肪组织湿重与肥胖错义组差异未达到统计学意义外，其余指标与肥胖盐水组、肥胖错义组相比差异均有显著性，而肥胖错义组与肥胖盐水组之间各观察指标差异均无显著性。结论 侧脑室注射NPY Y5受体基因反义寡核苷酸可显著减少营养性肥胖大鼠的腹膜后脂肪，降低肥胖大鼠脂肪组织ob基因表达及血清瘦素、胰岛素含量，改善外周瘦素抵抗。     

Expression of functional Y1 receptors for neuropeptide Y in human Ewing's sarcoma cell lines

Summary In the human Ewing's sarcoma cell line WE-68, saturation analysis using³H-labelled neuropeptide Y ([³H]NPY) as the radioligand disclosed a homogeneous population of binding sites with a dissociation constant (K _d ) of 4.5 nM and maximal binding capacity (B _max) of 712 fmol/mg cell protein. Besides the WE-68 cell line, ten other human Ewing's sarcoma cell lines (FM-62, HS-80, HT-78, HT-M1-78, NT-68, RM-82, RS-63, VH-64, WE-M1-68, WE-M2-68) were also found to display NPY receptors withK _d varying from 3.5 nM to 10.7 nM andB _max=247–3744 fmol/mg cell protein. NPY, its natural analogues and the Y₁-receptor-specific peptide ligand [Leu³¹, Pro³⁴]NPY inhibited [³H]NPY binding in the potency order: [Leu³¹,Pro³⁴]NPYhuman NPYpeptide YY (PYY)>> salmon pancreatic polypeptide (PP) > human PP>porcine NPY_13–36NPY_22–36. In the Ewing's sarcoma cell lines NPY provoked inhibition of forskolin-stimulated cyclic AMP formation by up to 98%. Pertussis toxin alleviated the cyclic-AMP-inhibitory response to NPY. In isolated Ewing's sarcoma plasma membranes pertussis toxin [³²P]ADP-ribosylated a 41-kDa protein. The ability of NPY and analogues to inhibit cyclic AMP accumulation paralleled their potencies in displacing radioligand binding. By contrast, a cell line derived from an atypical form of Ewing's sarcoma did not express specific and functional NPY receptors. These results demonstrate that conventional Ewing's sarcoma cells possess G_i-potein-coupled NPY receptors of the Y₁ type, which upon interaction with NPY, PYY, and PP mediate inhibition of cyclic AMP generation.Abbreviations NPY neuropeptide Y - PP pancreatic polypeptide - PYY peptide YY - VIP vasoactive intestinal peptide     

Increasing trends in incidence of overweight and obesity over 5 decades

Purpose

We evaluated trends in the incidence of overweight and obesity over the past 50 years.

Methods

We evaluated trends in the incidence of overweight (25 ≤ body mass index [BMI] <30 kg/m²), obesity (BMI ≥30 kg/m²) and stage 2 obesity (BMI ≥35 kg/m²) from 1950 to 2000 in Framingham Study participants (n = 6798, 54% women). Individuals aged 40-55 years who attended 2 examinations 8 years apart in each decade were eligible.

Results

The incidences of overweight, obesity, and stage 2 obesity increased across the decades in both sexes (P for trend <.001). For men, the incidence of overweight rose from 21.8% (95% confidence interval [CI], 17.6-26.5) in the 1950s to 35.2% (95% CI, 28.6-42.5) in the 1990s; of obesity from 5.8% (95% CI, 4.4-7.6) to 14.8% (95% CI, 12.2-17.9); and of stage 2 obesity from 0.2% (95% CI, 0.1-0.9) to 5.4% (95% CI, 4.0-7.2). For women, incidence rates of overweight increased from 15.0% (95% CI, 12.3-18.1) to 33.1% (95% CI, 29.0-37.4); of obesity from 3.9% (95% CI, 2.9-5.3) to 14% (95% CI, 11.6-16.7); and of stage 2 obesity from 1.7% (95% CI, 1.1-2.6) to 4.4% (95% CI, 3.2-6.0). Overall, incidence rates of overweight increased 2-fold and that of obesity more than 3-fold over 5 decades, findings that remained robust upon additional adjustment for baseline BMI in each decade.

Conclusions

The incidence of overweight and obesity increased progressively over the last 5 decades, suggesting that the rising trend in prevalence is not a recent phenomenon.