鱼类leptin的生物学特性及功能

瘦素(Leptin)是肥胖基因(Obese gene)的产物, 属于I型细胞因子。在哺乳动物中, leptin主要由脂肪细胞合成与分泌, 是调控摄食、能量代谢、骨骼发育、甲状腺功能以及繁殖等生理过程的重要激素。目前, 多种硬骨鱼类的leptin基因已被克隆, 其功能也已得到初步研究。研究认为, 鱼类leptin的主要合成部位在肝脏, 其在氨基酸序列上与哺乳动物存在很大差异, 但蛋白质结构高度保守; 功能方面, leptin可调节鱼类的摄食、葡萄糖和脂肪代谢以及繁殖等生命活动过程。本文就鱼类leptin及其受体的特征结构、组织分布、表达调控及功能研究进展进行简要综述。       

瘦蛋白对摄食和能量平衡的调节及其在哺乳动物冬眠中的作用

白色脂肪合成和分泌的瘦蛋白(leptin)作用于下丘脑和外周的代谢产热器官,对摄食和能量平衡起调节作用。摄食和能量平衡的失调,如瘦蛋白抵抗,可以导致肥胖等一系列生理疾病。以体内贮存的脂肪为主要能源物质越冬的冬眠哺乳动物,体重的年周期波动幅度巨大,其摄食和能量平衡调节机制可能不同于一般的非冬眠物种,育肥阶段可能存在瘦蛋白抵抗机制。本文总结了瘦蛋白调节摄食和能量平衡的作用机制以及瘦蛋白对冬眠哺乳动物育肥和冬眠的影响,为进一步研究冬眠哺乳动物的能量平衡提供参考。     

Kisspeptins/GPR54神经内分泌系统对哺乳动物生殖活动的调控

哺乳动物的生殖活动受到神经内分泌系统的精确调控。近年来的研究表明,KISS-1基因的表达产物Kisspeptins及其G蛋白偶联受体（G protein coupled receptor 54,GPR54）在这一调控网络中发挥着重要作用,与哺乳动物青春期启动、发情排卵及季节性繁殖等过程密切相关。该文就近年来Kisspeptins/GPR54系统对哺乳动物生殖活动调控的研究进展进行简述。     

Apelin/APJ调节鱼类摄食的研究进展

Apelin是1998年首次从牛胃分泌物中提取出的APJ的内源性配体,Apelin及其受体APJ广泛分布于动物中枢和外周组织中。Apelin通过与受体APJ结合,不仅参与血压调节、痛觉调节、体液平衡和细胞凋亡等多种生理过程,还在动物摄食调控和胃肠道运动调节中发挥重要作用。目前,关于Apelin调控摄食的作用还存在争议。现依据Apelin和APJ在哺乳动物和鱼类的研究进展,阐述Apelin及APJ的结构、组织分布和对动物摄食的调控及其机制,以期为其在鱼类摄食调控方面的研究提供参考。     

牦牛LIFR 基因的克隆及其在繁殖周期卵巢中的表达

白血病抑制因子受体(LIFR)与白血病抑制因子(LIF)结合,在排卵、胚胎发育及胚胎附植等过程中起重要的调节作用,与哺乳动物生殖过程密切相关。为进一步研究白血病抑制因子受体(LIFR)基因在卵巢中的表达,本研究对牦牛LIFR 基因进行克隆和序列分析,并利用RT-PCR 技术研究其在繁殖周期卵巢中的表达情况。本研究克隆得到牦牛3 329 bp 的LIFR 基因cDNA 序列,内含3 288 bp 开放阅读框序列。与家牛的相应序列具有很高的同源性(99 5% ),表明LIFR 基因在进化过程中较为保守。实时定量RT-PCR 检测LIFR 基因在繁殖周期卵巢中的表达,结果显示卵巢中LIFR 基因在妊娠期表达最强。表明LIFR 基因在牦牛繁殖周期中具有不可忽视的作用。     

草鱼与鲢鱼肥胖基因克隆与序列分析

肥胖基因产物leptin是调节哺乳动物摄食、能量代谢等生命活动的重要细胞因子。 应用RT-PCR和RACE法获得了草鱼(Ctenopharyngodon idellus)和鲢鱼(Hypophthalmichthys molitrix) leptin基因的全长cDNA序列分别为1 096 bp和1 176 bp,编码173和172个氨基酸。氨基酸序列同源性分析表明,草鱼和鲢鱼的leptin序列与其它鲤科鱼类leptin的同源性较高,而与其他鱼类的leptin同源性很低,但所有鱼类的leptin均含有用于形成二硫键的高度保守的半胱氨酸。系统进化树分析显示,草鱼和鲢鱼leptin与其他鱼类leptin聚于一进化分支。应用PCR和Genome Walker方法,进一步获得了草鱼和鲢鱼leptin基因的内含子和5′侧翼区序列。结果表明,获得的草鱼和鲢鱼leptin基因长度分别为2 129 bp和2 192 bp,含有与其他脊椎动物leptin相似的基因结构（含三个外显子和两个内含子）。本研究为深入研究鱼类肥胖基因结构功能关系与鱼类抗肥胖品系定向遗传选育奠定了良好的基础。     

瘦蛋白信号转导及瘦蛋白抵抗机制

瘦蛋白(leptin)通过结合瘦蛋白受体,启动信号转导,发挥控制摄食和调节能量代谢等重要神经内分泌调节功能。肥胖症患者血浆瘦蛋白水平普遍升高,存在瘦蛋白抵抗,瘦蛋白抵抗是导致肥胖症的关键因素。本文综述了瘦蛋白信号转导作用及瘦蛋白抵抗可能的机制。     

哺乳动物病毒共受体的特征研究

为了探究哺乳动物病毒共受体间的共性特征,本研究基于ViralReceptor数据库中收集的哺乳动物病毒-受体相互作用关系,共收集277对病毒共受体组合,从结构、功能、进化和组织表达等方面对这些病毒共受体进行系统分析,并与来源于不同哺乳动物的病毒受体组合以及随机挑选的人类蛋白组合进行比较。结果显示,哺乳动物病毒共受体相较于其他蛋白组合,彼此间有更高的功能相似性,在宿主蛋白相互作用网络中相互作用的比例更高,在人体常见组织中的共表达水平更高。研究表明,哺乳动物病毒共受体具有功能、表达和互作等共性特征。期望此结果能为病毒受体的发现和鉴定等研究提供参考。     

脂联素及其受体在哺乳动物中的研究进展与展望

脂肪组织分泌的一种内源性细胞因子—脂联素,在其受体的作用下,参与机体的能量平衡、葡糖糖代谢、脂肪酸氧化、抗炎、胰岛素拮抗等方面的调节,发挥着重要的生物学功效。就脂联素及其受体的结构特征、表达调控及多态性,针对提高哺乳动物的生长与繁殖性能,降低哺乳动物体内的脂肪沉积等问题作一综述。     

用PCR-RFLP法分析绵羊4品种褪黑激素受体1a基因第二外显子

近几年的研究表明,裉黑激素通过与高亲和性G蛋白耦联受体结合,调节哺乳动物的季节性昼夜繁殖节律和繁殖变化,同时还发现内切酶MnlI酶切位点的基因型与Merinos d’Arles母绵羊季节性不排卵活动相关联。为此,为提高绵羊的繁殖率,扬州大学季从亮博士、中国农科院畜牧所储明星研究员和聊城大学周国利先生等用PCRRFLP分析法对4个绵羊（小尾寒羊、湖羊、多赛特羊和萨福克羊共146只）褪黑激素受体1a基因第二外显子作了研究。     

Leptin receptor in the chicken ovary: potential involvement in ovarian dysfunction of ad libitum-fed broiler breeder hens

In hens, the ovarian follicles committed to ovulation are arranged in an ordered follicular hierarchy. In standard broiler breeders hens genetically selected for high growth rate the reproductive function is clearly dysfunctional. Feed restriction is needed during reproductive development to limit the formation of excessive numbers of ovarian yellow follicles arranged in multiple hierarchies. To determine whether leptin is involved in the nutritional and reproductive interactions controlling follicular hierarchy in hens, blood leptin levels and ovarian expression of the leptin receptor mRNA were determined during follicle maturation in three chicken lines; a slow growing broiler "Label" genotype without reproductive dysfunction, a fast growing "Standard" genotype fed ad libitum or restricted and a fast growing "Experimental" line with intermediate reproductive performance levels. Whereas expression of the leptin receptor mRNA did not change in the theca, it clearly decreased with follicular differentiation in the granulosa of slow growing hens. In fast growing standard hens fed ad libitum and presenting significant reproductive dysfunction, the decrease was disrupted and dramatic up-regulation of granulosa cell expression of the leptin receptor was observed. On the other hand, feed restriction decreased the overall level of expression of the leptin receptor mRNA and restored the decrease with follicular growth. The level of expression of the leptin receptor probably modulates the action of leptin on follicular differentiation. Since blood leptin and other metabolic factors were not affected by the genotype or by nutritional state, the factors involved in the regulation of leptin receptor gene expression remain to be determined. This study demonstrates the involvement of leptin in the nutritional control of reproduction in birds. Leptin action on the ovary probably controls follicular hierarchy through the regulation of steroidogenesis.     

Opportunism, photoperiodism, and puberty: Different mechanisms or variations on a theme?

There are many parallels between the neural regulation of seasonal breeding in birds and puberty in primates, but most studies of the regulation of puberty in vertebrates involve the use of rodents. The findings from rodent studies are often perceived as being typical of mammals and therefore pertinent to human reproductive biology and in many cases, rodent models have a great deal to offer in terms of an understanding of the regulation of puberty and reproductive biology. However, knowledge available from comparative work perhaps highlights mechanistic similarities that may not exist between rodent and primate systems. In this short review, we highlight some of the advantages of studying avian reproductive biology in this regard. We discuss disparities between rodent puberty and primate puberty, and similarities between primates and birds. Thus, understanding the mechanisms regulating avian puberty and seasonal breeding might in some cases provide greater insight into the mechanistic control of puberty in nonrodent mammals. We also describe in detail the neuroendocrine regulation of reproduction in birds and aim to provoke discussion of the possible roles of thyroid hormones and multiple forms of gonadotropin-releasing hormone in avian and mammalian reproduction.     

Vertebrate ancient opsin photopigment spectra and the avian photoperiodic response

In mammals, photoreception is restricted to cones, rods and a subset of retinal ganglion cells. By contrast, non-mammalian vertebrates possess many extraocular photoreceptors but in many cases the role of these photoreceptors and their underlying photopigments is unknown. In birds, deep brain photoreceptors have been shown to sense photic changes in daylength (photoperiod) and mediate seasonal reproduction. Nonetheless, the specific identity of the opsin photopigment 'sensor' involved has remained elusive. Previously, we showed that vertebrate ancient (VA) opsin is expressed in avian hypothalamic neurons and forms a photosensitive molecule. However, a direct functional link between VA opsin and the regulation of seasonal biology was absent. Here, we report the in vivo and in vitro absorption spectra (λ(max) = ~490 nm) for chicken VA photopigments. Furthermore, the spectral sensitivity of these photopigments match the peak absorbance of the avian photoperiodic response (λ(max) = 492 nm) and permits maximum photon capture within the restricted light environment of the hypothalamus. Such a correspondence argues strongly that VA opsin plays a key role in regulating seasonal reproduction in birds.     

鸟类的周期性繁殖及其神经内分泌机制

大多数鸟类的繁殖活动具有明显的周期性。影响鸟类繁殖活动的主要因素是光周期 ,传统观点认为可促进繁殖活动的长日照能导致许多鸟类的生殖系统处于光不应状态 ;非光周期因素如食物的多寡、环境温度等其它条件也可影响特殊生活环境中的鸟类的繁殖活动。鸟类的周期性繁殖是环境因素导致神经内分泌过程改变的结果 ,受下丘脑 垂体 性腺轴的调节 ,其中下丘脑的促性腺激素释放激素(GnRH)起重要作用     

Manipulation of life-history decisions using leptin in a wild passerine

Seasonal timing of reproduction and the number of clutches produced per season are two key avian life-history traits with major fitness consequences. Female condition may play an important role in these decisions. In mammals, body condition and leptin levels are correlated. In birds, the role of leptin remains unclear. We did two experiments where we implanted female great tits with a pellet releasing leptin evenly for 14 days, to manipulate their perceived body condition, or a placebo pellet. In the first experiment where females were implanted when feeding their first brood offspring we found, surprisingly, that placebo treated females were more likely to initiate a second brood compared to leptin treated females. Only one second brood fledged two chicks while five were deserted late in the incubation stage or when the first egg hatched. No difference was found in female or male return rate or in recruitment rate of fledglings of the first brood, possibly due to the desertion of the second broods. In our study population, where there is selection for early egg laying, earlier timing of reproduction might be hampered by food availability and thus nutritional state of the female before egg laying. We therefore implanted similar leptin pellets three weeks before the expected start of egg laying in an attempt to manipulate the laying dates of first clutches. However, leptin treated females did not initiate egg laying earlier compared to placebo treated females, suggesting that other variables than the perceived body condition play a major role in the timing of reproduction. Also, leptin treatment did not affect body mass, basal metabolic rate or feeding rates in captive females. Manipulating life history decisions using experimental protocols which do not alter individuals' energy balance are crucial in understanding the trade-off between costs and benefits of life history decisions.     

Ecological,evolutionary, and conservation implications of incubation temperature‐dependent phenotypes in birds

Incubation is a vital component of reproduction and parental care in birds. Maintaining temperatures within a narrow range is necessary for embryonic development and hatching of young, and exposure to both high and low temperatures can be lethal to embryos. Although it is widely recognized that temperature is important for hatching success, little is known about how variation in incubation temperature influences the post‐hatching phenotypes of avian offspring. However, among reptiles it is well known that incubation temperature affects many phenotypic traits of offspring with implications for their future survival and reproduction. Although most birds, unlike reptiles, physically incubate their eggs, and thus behaviourally control nest temperatures, variation in temperature that influences embryonic development still occurs among nests within a population. Recent research in birds has primarily been limited to populations of megapodes and waterfowl; in each group, incubation temperature has substantial effects on hatchling phenotypic traits important for future development, survival, and reproduction. Such observations suggest that incubation temperature (and incubation behaviours of parents) is an important but underappreciated parental effect in birds and may represent a selective force instrumental in shaping avian reproductive ecology and life‐history traits. However, much more research is needed to understand how pervasive phenotypic effects of incubation temperature are among birds, the sources of variation in incubation temperature, and how effects on phenotype arise. Such insights will not only provide foundational information regarding avian evolution and ecology, but also contribute to avian conservation.     

Contribution of BDNF-mediated inhibition in patterning avian skin innervation

Multiple factors are involved in the development and regulation of sensory innervation in skin. The findings we report here suggest that brain-derived neurotrophic factor (BDNF)-mediated inhibition may play an important role in determining the pattern of sensory innervation in avian skin. In birds, cutaneous innervation is restricted to dermis, where axons form a ring of innervation around the base of each feather. Here we show that both BDNF message and protein are more abundant in avian epidermis than dermis when innervation is being established; the BDNF in dermis is localized to feather buds. In vitro, BDNF caused growth cones of NGF-dependent dorsal root ganglion neurons to collapse. Similarly, outgrowth of neurites toward BDNF-secreting fibroblasts was inhibited. The inhibitory effects of BDNF appear to be mediated by the low-affinity p75 neurotrophin receptor, rather than a trk receptor. Thus, the distribution of BDNF in embryonic avian skin and the inhibitory effects of BDNF on cutaneous neurites in vitro suggest that BDNF may be important in restricting axons from entering the epidermis and the core of feather buds during development in vivo.