The ontogeny of leptin mRNA expression in growing broilers and its relationship to metabolic body weight.

The polypeptide hormone leptin is produced by both adipose tissue and the liver and has been shown to induce satiety in chickens. In this study we have investigated the developmental regulation of leptin mRNA expression in growing broiler chickens. Leptin expression generally increases in all tissues from 1-12 weeks of age. In the subcutaneous fat depot there is an apparent pattern of increased leptin mRNA expression occurring at 2, 6, and 10 weeks post-hatch. This pattern was not evident in the other tissues surveyed and may relate to the cycle of loading and unloading of adipocytes with lipid. No consistent gender differences in leptin expression patterns were detected in the tissues surveyed, as is often observed in mammals. Positive correlations between metabolic body weight and adipose leptin expression levels were observed. Leptin expression by the liver was highly correlated with metabolic body weight from 1-6 weeks of age, and uncorrelated from 6-12 weeks of age. This pattern of increasing liver leptin expression with increasing body weight during the early rapid growth phase of the bird may be due to limited fat storage during this period, which is followed by rapid body fat accumulation from 6-12 weeks. The characterization and tissue specific distribution of leptin mRNA expression in the growing broiler indicate similar patterns of leptin production to that of growing mammals. Leptin may be involved in lipid flux through the adipocyte as well as the shift in lipid metabolism to increased storage during pre-puberty.     

Leptin和下丘脑一垂体-性腺轴

Leptin是一种主要由脂肪组织分泌的蛋白质类激素，广泛存在于各组织、器官中。它可通过调节能量代谢来保持体脂相对稳定。近年来研究发现，Leptin作为一种代谢信号对下丘脑－垂体－性腺轴的调节功能发挥着重要作用。其可以调节胎儿胎盘和子宫代谢，可以使动物提前发情，缩短发情周期，因此，在提高动物繁殖性能上有重要的应用价值。     

Biology of leptin in the pig

The recently discovered protein, leptin, which is secreted by fat cells in response to changes in body weight or energy, has been implicated in regulation of feed intake, energy expenditure and the neuroendocrine axis in rodents and humans. Leptin was first identified as the gene product found deficient in the obese ob/ob mouse. Administration of leptin to ob/ob mice led to improved reproduction as well as reduced feed intake and weight loss. The porcine leptin receptor has been cloned and is a member of the class 1 cytokine family of receptors. Leptin has been implicated in the regulation of immune function and the anorexia associated with disease. The leptin receptor is localized in the brain and pituitary of the pig. The leptin response to acute inflammation is uncoupled from anorexia and is differentially regulated among swine genotypes. In vitro studies demonstrated that the leptin gene is expressed by porcine preadipocytes and leptin gene expression is highly dependent on dexamethasone induced preadipocyte differentiation. Hormonally driven preadipocyte recruitment and subsequent fat cell size may regulate leptin gene expression in the pig. Expression of CCAAT-enhancer binding protein (C/EBP) mediates insulin dependent preadipocyte leptin gene expression during lipid accretion. In contrast, insulin independent leptin gene expression may be maintained by C/EBP auto-activation and phosphorylation/dephosphorylation. Adipogenic hormones may increase adipose tissue leptin gene expression in the fetus indirectly by inducing preadipocyte recruitment and subsequent differentiation. Central administration of leptin to pigs suppressed feed intake and stimulated growth hormone (GH) secretion. Serum leptin concentrations increased with age and estradiol-induced leptin mRNA expression in fat was age and weight dependent in prepuberal gilts. This occurred at the time of expected puberty in intact contemporaries and was associated with greater LH secretion. Further work demonstrated that leptin acts directly on pituitary cells to enhance LH and GH secretion, and brain tissue to stimulate gonadotropin releasing hormone secretion. Thus, development of nutritional schemes and (or) gene therapy to manipulate leptin secretion will lead to practical methods of controlling appetite, growth and reproduction in farm animals, thereby increasing efficiency of lean meat production.     

Circulating leptin and its muscle gene expression in Nellore cattle with divergent feed efficiency

Background: Leptin has a strong relation to important traits in animal production, such as carcass composition,feed intake, and reproduction. It is mainly produced by adipose cells and acts predominantly in the hypothalamus.In this study, circulating leptin and its gene expression in muscle were evaluated in two groups of young Nellore bulls with divergent feed efficiency. Individual dry matter intake(DMI) and average daily gain(ADG) of 98 Nellore bulls were evaluated in feedlot for 70 d to determinate the residual feed intake(RFI) and select 20 animals for the high feed efficient(LRFI) and 20 for the low feed efficient(HRFI) groups. Blood samples were collected on d 56 and at slaughter(80 d) to determine circulating plasma leptin. Samples of Longissimus dorsi were taken at slaughter for leptin gene expression levels.Results: DMI and RFI were different between groups and LRFI animals showed less back fat and rump fat thickness,as well as less pelvic and kidney fat weight. Circulating leptin increased over time in all animals. Plasma leptin was greater in LRFI on 56 d and at slaughter(P = 0.0049). Gene expression of leptin were greater in LRFI animals(P = 0.0022) in accordance with the plasma levels. The animals of the LRFI group were leaner, ate less, and had more circulating leptin and its gene expression.Conclusion: These findings demonstrated that leptin plays its physiological role in young Nellore bulls, probably controlling food intake because feed efficient animals have more leptin and lower residual feed intake.     

Leptin的生物学功能及其对脂肪沉积的调控作用

Leptin（瘦素）是肥胖基因ob基因的表达产物,由脂肪细胞分泌,与下丘脑Leptin受体结合,可抑制食欲中枢,减少进食量,并通过兴奋交感神经系统,促进脂肪分解,增加产热,从而发挥降低体重,提高瘦肉率的功能。对Leptin的生物学功能及其对脂肪沉积的调控作用进行综述,以期为营养上调控畜禽肉品质,以及生产优质畜禽产品提供理论依据和科研基础。     

Role of leptin in farm animals: a review

The discovery of hormone leptin has led to better understanding of the energy balance control. In addition to its effects on food intake and energy expenditure, leptin has now been implicated as a mediator of diverse physiological functions. Recently, leptin has been cloned in several domestic species. The sequence similarity suggests a common function or mechanism of this peptide hormone across species. Leptin receptors are expressed in most of tissues, which is consistent with the multiplicity of leptin functions. The main goal of this review was to summarize knowledge about effect of leptin on physiology of farm animals. Experiments point to a stimulatory action of leptin on growth hormone (GH) secretion, normal growth and development of the brain. Surprisingly, leptin is synthesized at a high rate in placenta and may function as a growth factor for fetus, signalling the nutritional status from the mother to her offspring. Maturation of reproductive system can be stimulated by leptin administration. Morphological and hormonal changes, consistent with a major role of leptin in the reproductive system, have also been described, including the stimulation of the release of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. Leptin has a substantial effect on food intake and feeding behaviour in animals. Administration of leptin reduces food intake. Its level decrease within hours after initiation of fasting. Leptin also serves as a mediator of the adaptation to fasting, and this role may be the primary function for which was the molecule evolved.     

Fat depot‐specific differences in leptin mRNA expression and its relation to adipocyte size in steers

ABSTRACT This experiment was conducted to investigate leptin mRNA expression, adipocyte size, and their relationship in several adipose tissues of fattening steers. Subcutaneous, perirenal, intermuscular and intramuscular adipose tissues were collected from three crossbred steers (Japanese Black cattle X Holstein) aged 21 months. The mRNA level and adipocyte diameter were determined in these adipose tissues. The intramuscular adipose tissue had a lower leptin mRNA level than the intermuscular and perirenal adipose tissues (P < 0.05). Leptin mRNA level was lower in the subcutaneous depot than in the intermuscular depot (P < 0.05). Adipocyte diameter was larger in the intermuscular adipose tissue than in the subcutaneous and intramuscular adipose tissues (P < 0.05). Leptin mRNA level was positively correlated with adipocyte diameter (r² = 0.81, P < 0.05). These results suggest that the cattle have fat depot‐specific differences in leptin gene expression, which are a result of a difference in adipocyte size.     

Leptin: a metabolic signal affecting central regulation of reproduction in the pig

The discovery of the obesity gene and its product, leptin, it is now possible to examine the relationship between body fat and the neuroendocrine axis. A minimum percentage of body fat may be linked to onset of puberty and weaning-to-estrus interval in the pig. Adipose tissue is no longer considered as only a depot to store excess energy in the form of fat. Recent findings demonstrate that numerous genes, i.e., relaxin, interleukins and other cytokines and biologically active substances such as leptin, insulin-like growth factor-I (IGF-I), IGF-II and Agouti protein are produced by porcine adipose tissue, which could have a profound effect on appetite and the reproductive axis. Hypothalamic neurons are transsynaptically connected to porcine adipose tissue and may regulate adipose tissue function. In the pig nutritional signals such as leptin are detected by the central nervous system (CNS) and translated by the neuroendocrine system into signals, which regulate appetite, hypothalamic gonadotropin-releasing hormone (GnRH) release and subsequent luteinizing hormone (LH) secretion. Furthermore, leptin directly affects LH secretion from the pituitary gland independent of CNS input. Changes in body weight or nutritional status are characterized by altered adipocyte function a reduction in adipose tissue leptin expression, serum leptin concentrations and a concurrent decrease in LH secretion. During pubertal development serum leptin levels, hypothalamic leptin receptor mRNA and estrogen-induced leptin gene expression in fat increased with age and adiposity in the pig and this occurred at the time of expected puberty. In the lactating sow serum and milk leptin concentrations were positively correlated with backfat thickness and level of dietary energy fed during gestation as well as feed consumption. Although, these results identify leptin as a putative signal that links metabolic status and neuroendocrine control of reproduction, other adipocyte protein products may play an important role in regulating the reproductive axis in the pig.     

Leptin expression in ruminants: nutritional and physiological regulations in relation with energy metabolism

Leptin, mainly produced in adipose tissue (AT), is a protein involved in the central and/or peripheral regulation of body homeostasis, energy intake, storage and expenditure, fertility and immune functions. Its role is well documented in rodent and human species, but less in ruminants. This review is focused on some intrinsic and extrinsic factors which regulate adipose tissue leptin gene expression and leptinemia in cattle, sheep, goat and camel: age, physiological status (particularly pregnancy and lactation) in interaction with long-term (adiposity) and short-term effects of feeding level, energy intake and balance, diet composition, specific nutrients and hormones (insulin, glucose and fatty acids), and seasonal non-dietary factors such as photoperiod. Body fatness strongly regulates leptin and its responses to other factors. For example, leptinemia is higher after underfeeding or during lactation in fat than in lean animals. Physiological status per se also modulates leptin expression, with lactation down-regulating leptinemia, even when energy balance (EB) is positive. These results suggest that leptin could be a link between nutritional history and physiological regulations, which integrates the animal's requirements (e.g., for a pregnancy-lactation cycle), predictable food availability (e.g., due to seasonal variations) and potential for survival (e.g., body fatness level). Reaching permissive leptin thresholds should be necessary for pubertal or postpartum reproductive activity. In addition to the understanding of leptin yield regulation, these data are helpful to understand the physiological significance of changes in leptin secretion and leptin effects, and how husbandry strategies could integrate the adaptative capacities of ruminant species to their environment.     

Leptin in ruminants. Gene expression in adipose tissue and mammary gland, and regulation of plasma concentration

This paper reviews data on leptin gene expression in adipose tissue (AT) and mammary gland of adult ruminants, as well as on plasma leptin variations, according to genetic, physiological, nutritional and environmental factors. AT leptin mRNA level was higher in sheep and goat subcutaneous than visceral tissues, and the opposite was observed in cattle; it was higher in fat than in lean selection line in sheep; it was decreased by undernutrition and increased by refeeding in cattle and sheep, and not changed by adding soybeans to the diet of lactating goats; it was increased by injection of NPY to sheep, and by GH treatment of growing sheep and cattle. Insulin and glucocorticoids in vitro increased AT leptin mRNA in cattle, and leptin production in sheep. Long daylength increased AT lipogenic activities and leptin mRNA, as well as plasma leptin in sheep. Mammary tissue leptin mRNA level was high during early pregnancy and was lower but still expressed during late pregnancy and lactation in sheep. Leptin was present in sheep mammary adipocytes, epithelial and myoepithelial cells during early pregnancy, late pregnancy and lactation, respectively. Plasma leptin in cattle and sheep was first studied thanks to a commercial “multi-species” kit. It was positively related to body fatness and energy balance or feeding level, and decreased by β-agonist injection. The recent development of specific RIA for ruminant leptin enabled more quantitative study of changes in plasma leptin concentration, which were explained for 35–50% by body fatness and for 15–20% by feeding level. The response of plasma leptin to meal intake was related positively to glycemia, and negatively to plasma 3-hydroxybutyrate. The putative physiological roles of changes in leptin gene expression are discussed in relation with published data on leptin receptors in several body tissues, and on in vivo or in vitro effects of leptin treatment.     

瘦素对动物初情期启动的调控

瘦素是一种主要由脂肪组织分泌的蛋白质激素，瘦素不仅调节体内的能量平衡，而且影响动物的生殖。它传递体内的营养状态和能量储存信号对中枢神经系统，在调控动物初情期启动的时间上占据一定的地位，但瘦素的作用机理目前还不清楚。     

瘦素对动物生殖调控的研究进展

瘦素是由白色脂肪细胞分泌的一种蛋白类激素,对动物的采食量及能量平衡调控具有明显的作用。除此之外,瘦素对生殖系统也有着重要的调节作用。瘦素通过JAK-STAT途径及与KiSS-1/GPR54系统的相互作用,对动物初情期的启动,下丘脑—垂体—性腺(HPG)轴及胎盘与子宫等产生广泛的影响。     

动物肥胖基因（ob）的研究进展

肥胖基因（ob）调节动物生长和维持能量平衡的生物学功能都是通过其产物——瘦素蛋白（Leptin）来实现的.因此,控制Leptin在动物体内的表达水平可有效降低脂肪含量,提高瘦肉率,从而为畜牧产业带来可观的经济效益.就ob基因的研究进展进行了系统性的综述.     

Effect of polymorphisms linked to LEP gene on its expression on adipose tissues in beef cattle

In cattle, genetic markers at the leptin (LEP) gene and at those linked to the gene have been described as affecting calving interval (markers LEPSau3AI and IDVGA51), or daily weight gain (BMS1074 and BM1500). This work investigated the effect of these alleles on LEP mRNA levels in cattle subcutaneous and omental adipose tissues. A sample of 137 females of a Brangus‐Ibage beef cattle herd was analysed to evaluate the distribution of the polymorphisms; then, animals having at least one of the IDVGA51*181 (allele 181 at marker IDVGA51; six animals), LEPSau3AI*2 (four), BMS1074*151 (13), BM1500*135 (six) alleles and a control group composed of animals without any of these alleles (four animals) were submitted to surgery to obtain omental and subcutaneous adipose tissues. Leptin mRNA expression was quantified by TaqMan RT‐PCR, using 18S rRNA as internal control and adjusted for the effect of body condition score, through regression analysis. Omental fat had LEP gene expression 33% lower than the subcutaneous tissue. Carriers of IDVGA*181 and BMS1074*151 showed subcutaneous fat leptin mRNA levels higher than the controls. Leptin controls feed intake and coordinates reproduction; therefore, animals with higher LEP gene expression will probably have lower daily weight gain than others with similar forage offer and nutritional condition and probably will also have longer calving interval.