<!DOCTYPE html>
<html xmlns="http://www.w3.org/1999/xhtml">
	<head>
		<meta charset="utf-8" />
		<title>AAVS_MH20141211011229_Saleem et al</title>
		<link href="http://nexusacademicpublishers.com/uploads/cssfiles/AAVS_MH20141211011229_Saleem et al.css" rel="stylesheet" type="text/css" />
	</head>
	<body id="AAVS_MH20141211011229_Saleem-et-al" xml:lang="en-US">
		<div class="Basic-Text-Frame">
			<p class="Type-of-Article" xml:lang="en-GB">&nbsp;</p>
			<p class="Type-of-Article" xml:lang="en-GB">&nbsp;</p>
			<p class="Type-of-Article" xml:lang="en-GB"><span class="CharOverride-1">Review Article</span></p>
		</div>
		<div class="Basic-Text-Frame">
			<p class="title- ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="title- ParaOverride-1" xml:lang="en-GB">Role of Leptin in Growth, Reproduction and Milk Production in Farm Animals: A Review</p>
		</div>
		<div class="Basic-Text-Frame">
			<p class="Authors ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Authors ParaOverride-1" xml:lang="en-GB"><span class="CharOverride-2">Ali Haider Saleem</span><span class="CharOverride-3">1</span><span class="CharOverride-2">, Tanveer Hussain</span><span class="CharOverride-3">2*</span><span class="CharOverride-2">, Muhammad Zahid Tahir</span><span class="CharOverride-3">1</span><span class="CharOverride-2">, Asad Ali</span><span class="CharOverride-3">1</span><span class="CharOverride-2">, Waqas Ahmad Khan</span><span class="CharOverride-3">3</span><span class="CharOverride-2">, Muhammad Dawood</span><span class="CharOverride-3">1</span><span class="CharOverride-2">, Rizwan Ali</span><span class="CharOverride-3">1</span><span class="CharOverride-2">, Zia ur Rehman</span><span class="CharOverride-3">4</span></p>
		</div>
		<div class="Basic-Text-Frame">
			<p class="Affiliations ParaOverride-1" xml:lang="en-GB"><span class="CharOverride-4">1</span>University of Veterinary and Animal Sciences, Lahore, Pakistan; <span class="CharOverride-4">2</span>Virtual University of Pakistan, Lahore; <span class="CharOverride-4">3</span>University of Sargodha, Sargodha, Pakistan; <span class="CharOverride-4">4</span>Massey University, Palmerston North, New Zealand.</p>
		</div>
		<div>
			<p class="Abstract ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Abstract ParaOverride-1" xml:lang="en-GB"><span class="CharOverride-5">Abstract</span> | Livestock species of agri-based countries, like Pakistan, need special attention for the improvement and sustainability of their productive traits because the economy and huge population is largely dependent on livestock. Therefore it is necessary to adopt some strategies to get more adaptive and productive animals. Leptin, a hormone produced mostly by white adipose tissues of body, has many roles including body energy balance, tissue growth, body composition, reproduction and immunity. Leptin helps in reducing feed intake of animal through feed-back mechanism by informing CNS about body energy and fat reserves. The gene responsible for leptin production has many forms which are associated with leptin production, its level in blood and working. The physiological role of leptin and association of different forms of leptin (LEP) gene with multiple economic traits has made it a potential candidate to be studied and improve animals through proper breeding and management strategies. This current review article discusses the role of leptin in various economic traits of farm animals.</p>
		  <p class="Abstract ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Abstract ParaOverride-1" xml:lang="en-GB"><span class="CharOverride-5">Keywords </span>| Leptin, Growth, Reproduction, Milk production, Farm animals</p>
		</div>
		<div class="Basic-Text-Frame">
			<p class="Editor----Citation" xml:lang="en-GB"><span class="CharOverride-6">Editor</span> | Kuldeep Dhama, Indian Veterinary Research Institute, Uttar Pradesh, India.</p>
			<p class="Editor----Citation" xml:lang="en-GB"><span class="CharOverride-5">Received</span> | December  11, 2014; <span class="CharOverride-5">Revised</span> | January 05, 2015; <span class="CharOverride-5">Accepted</span> | January 06, 2015; <span class="CharOverride-5">Published</span> | May 04, 2015&#9;&#9;</p>
			<p class="Editor----Citation" xml:lang="en-GB"><span class="CharOverride-5">*Correspondence</span> | Tanveer Hussain, Virtual University of Pakistan, Lahore, Pakistan; <span class="CharOverride-5">Email:</span> tanveer.hussain@vu.edu.pk</p>
			<p class="Editor----Citation" xml:lang="en-GB"><span class="CharOverride-5">Citation</span> | Saleem AL, Hussain T, Tahir MZ, Ali A, Khan WA, Dawood M, Ali R, Rehman Z (2015). Role of leptin in growth, reproduction and milk production in farm animals: a review. Adv. Anim. Vet. Sci. 3(5): 302-307.  </p>
			<p class="Editor----Citation" xml:lang="en-GB"><span class="CharOverride-6">DOI</span><span class="CharOverride-7"> | </span><a href="http://dx.doi.org/10.14737/journal.aavs/2015/3.5.302.307"><span class="Hyperlink">http://dx.doi.org/10.14737/journal.aavs/2015/3.5.302.307</span></a></p>
			<p class="Editor----Citation" xml:lang="en-GB"><span class="Editor---Citation CharOverride-5" xml:lang="en-US">ISSN </span><span class="Editor---Citation CharOverride-5" xml:lang="en-US">(</span><span class="Editor---Citation CharOverride-5" xml:lang="en-US">Online</span><span class="Editor---Citation CharOverride-5" xml:lang="en-US">)</span> | 2307-8316; <span class="Editor---Citation CharOverride-5" xml:lang="en-US">ISSN </span><span class="Editor---Citation CharOverride-5" xml:lang="en-US">(Print)</span> | 2309-3331</p>
			<p class="Editor----Citation" xml:lang="en-GB"><span class="CharOverride-6">Copyright </span>© 2015 Saleem et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
		</div>
		<div class="Basic-Text-Frame">
			<p class="Heading-1--Introduction----" xml:lang="en-GB">&nbsp;</p>
		  <p class="Heading-1--Introduction----" xml:lang="en-GB">Introduction</p>
			<p class="Caps-on-First-Para ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Caps-on-First-Para ParaOverride-1" xml:lang="en-GB"><span class="_idGenDropcap-1">H</span><span>ormones </span>regulate various productive and reproductive traits in the body. The metabolism of energy in farm animals is controlled by a lot of hormonal factors like thyroid hormones and leptin. Leptin (Greek: <span class="CharOverride-8">leptos</span>=thin) is a 16 KDa peptide hormone and is generally produced in white adipose tissue. Its function is to signal the nervous system about the overall fat reserves of the body. It seems that leptin has a great influence in regulating whole body energy metabolism and may be attributed as a “metabolism modifier”. It is also accepted to be a biological marker that reflects the degree of fatness in the body. Leptin is encoded by LEP/ob gene, comprises of three exons and two introns and is located on 4<span class="CharOverride-9">th</span> and 5<span class="CharOverride-9">th</span> chromosome in cattle (<a href="#Pomp-D--Zou-T--Clutter-AC--Barendse-W--1997-."><span class="Hyperlink">Pomp et al., 1997</span></a>) and sheep, respectively. Among exons, only exon two and three are translated into protein (<a href="#Javanmard-A--Mohammadabadi-M--Zarrigabayi-G--Gharahedaghi-A--Nassiry-M--Javadmansh-A--Asadzadeh-N--2"><span class="Hyperlink">Javanmard et al., 2008</span></a>). It has been demonstrated that LEP gene affects reproduction and milk performance in cattle (<a href="#Nassiri-MR--Moussavi-AH--Alshawkany-A--Roudsari-SG--2007-."><span class="Hyperlink">Nassiri et al., 2007</span></a>). It also has key role in reproduction by regulating the secretion of gonadotropins in farm animals (<a href="#Barb-CR--Kraeling-RR--2004"><span class="Hyperlink">Barb and Kraeling, 2004</span></a>). Difference of LEP gene in human is shown to be related with low levels of leptin, obesity or over weight and non-insulin-dependent diabetes mellitus (<a href="#Van-der-Lende-T--te-Pas-MF--Veerkamp-R--Liefers-S--2005-."><span class="Hyperlink">Van der Lende et al., 2005</span></a>). Leptin has a role in regulating the energy balance when acts on nervous system (CNS) and affects deposition of fat in animals by controlling appetite and energy consumption (<a href="#Houseknecht-KL--Baile-CA--Matteri-RL--Spurlock-ME--1998"><span class="Hyperlink">Houseknecht et al., 1998</span></a>). Leptin, through its receptors in the peripheral tissues, has been involved in several roles, including lipid oxidation, glucose metabolism, endocrine system, angiogenesis, blood pressure, cell differentiation &amp; proliferation, brain development and wound healing (<a href="#Ahima-RS--Prabakaran-D--Mantzoros-C--Qu-D--Lowell-B--Maratos-Flier-E--Flier-JS--1996"><span class="Hyperlink">Ahima et al., 1996</span></a>; <a href="#Frank-S--Stallmeyer-B--Kampfer-H--Kolb-N--Pfeilschifter-J--2000-"><span class="Hyperlink">Frank et al., 2000</span></a>; <a href="#Agarwal-R--Rout-PK--Singh-SK--2009-"><span class="Hyperlink">Agarwal et al., 2009</span></a>). Leptin is also related with other living processes such as immune system, production of blood cells, bone producing cells and reproduction (<a href="#Olusi-S--Al-Awadhi-A--Abiaka-C--Abraham-M--George-S--2003-"><span class="Hyperlink">Olusi et al., 2003</span></a>; <a href="#Hafez-YM--2013"><span class="Hyperlink">Hafez, 2013</span></a>). Leptin can be in focus of interest in cattle because nutritional and metabolic disorders are major problems in this species.</p>
		  <p class="Caps-on-First-Para ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" xml:lang="en-GB">Action</p>
		  <p class="Heading-1--Introduction----" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">Research studies which stated that the food consumption of animals is regulated by the body fat content leaded the discovery of leptin (<a href="#Hossner-KL.-1998"><span class="Hyperlink">Hossner, 1998</span></a>). Leptin is chiefly synthesized by adipose tissues of body (<a href="#Kulig-H--Kmie--M--Kowalewska-Luczak-I--Andziak-G--2009-"><span class="Hyperlink">Kulig et al., 2009</span></a>) as the result of expression of LEP/ob gene and it has role in energy balance, fertility and immune response of individuals (<a href="#Hashemi-A--Mardani-K--Farhadian-M--Ashrafi-I--Ranjbari-M--2011"><span class="Hyperlink">Hashemi et al., 2011</span></a>). <a href="#Kennedy-GC--1953-."><span class="Hyperlink">Kennedy in 1953</span></a> proposed “lipostat” role of leptin which reflects its involvement in the regulation of body energy reserves. The physiology of leptin actions is all about its interactions with specific receptors in hypothalamus for energy regulation, its receptors exist in several forms; which can be divided into two broad classes, one with small cytoplasmic domains and other have a long cytoplasmic tail (<a href="#Hossner-KL--McCusker-RH--Dodson-MV--1997-."><span class="Hyperlink">Hossner et al., 1997</span></a>). The receptors with long cytoplasmic tail are considered to be the potential receptors that regulate most of leptin effects, acting through the JAK-STAT signal transduction pathway (<a href="#Hossner-KL.-1998"><span class="Hyperlink">Hossner, 1998</span></a>). While circulating in blood, leptin requires some binding proteins for increased half-life. In blood, it binds with three binding proteins with molecular weight 85, 176 and 240 KDa and the level of binding proteins in blood varies with genotype and feeding practices of individual (<a href="#Houseknecht-KL--Baile-CA--Matteri-RL--Spurlock-ME--1998"><span class="Hyperlink">Houseknecht et al. 1998</span></a>). <a href="#Sinha-MK--Opentanova-I--Ohannesian-JP--Kolaczynski-JW--Heiman-ML--Hale-J--Becker-GW--Bowsher-RR--Ste"><span class="Hyperlink">Sinha et al. (1996)</span></a> showed chromatographically the affinity of leptin with six binding proteins of molecular weight 68, 75, 80, 100, 130 and 280 KDa. Kidneys (renal medulla) are considered to be the organ of mammals where most of the plasma leptin is catabolize. Many studies showing the significant effectiveness of leptin when inserted in the lateral or third brain ventrical confirmed the primary site of leptin actions is central nervous system (<a href="#Geary-TW--McFadin-EL--MacNeil-MD--Grings-EF--Short-RR--Funston-RN--Keisler-DH--2003-."><span class="Hyperlink">Geary et al., 2003</span></a>). </p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" xml:lang="en-GB">LEP gene polymorphism</p>
		  <p class="Heading-1--Introduction----" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">Polymorphisms in the LEP gene of bovines has been described by <a href="#Lusk-JL--2007-"><span class="Hyperlink">Lusk (2007)</span></a>, <a href="#Shin-SC--Chung-ER--2007-.-Association-of-SNP-marker-in-the-leptin-gene-w"><span class="Hyperlink">Shin and Chung (2007)</span></a>, <a href="#Yang-D--Chen-H--Wang-X--Tian-Z--Tang-L--Zhang-Z--Lei-C--Zhang-L--Wang-Y--2007-"><span class="Hyperlink">Yang et al. (2007)</span></a> and <a href="#Guo-Y--Chen-H--Lan-X--Zhang-B--Pan-C--Zhang-L--Zhang-C--Zhao-M--2008-."><span class="Hyperlink">Guo et al. (2008)</span></a>. <a href="#Lagonigro-R--Wiener-P--Pilla-F--Woolliams-JA--Williams-JL--2003-"><span class="Hyperlink">Lagonigro et al. (2003)</span></a> and <a href="#Nkrumah-JD--Li-C--Yu-J--Hansen-C--Keisler-DH--Moore-SS--2005-"><span class="Hyperlink">Nkrumah et al. (2005)</span></a> studied its relationship with food intake. Association of leptin with meat quality and carcass traits has been demonstrated by <a href="#Schenkel-FS--Miller-SP--Ye-X--Moore-SS--Nkrumah-JD--Li-C--Yu-J--Mandell-IB--Wilton-JW--Williams-JL--"><span class="Hyperlink">Schenkel et al. (2005)</span></a>, <a href="#Boucher-D--Palin-MF--Castonguay-F--Gari-py-C--Pothier-F--2006"><span class="Hyperlink">Boucher et al. (2006)</span></a>, <a href="#Chung-ER--Shin-SC--Shin-KH--Chung-KY--2008"><span class="Hyperlink">Chung et al. (2008)</span></a>, <a href="#Kulig-H--Kmie--M--2009-"><span class="Hyperlink">Kulig and Kmieć (2009)</span></a>, <a href="#de-Oliveira-JA--Cunha-CMD--Crispim-BDA--Seno-LDO--Fernandes-ARM--Nogueira-GDP--Grisolia-AB--2013"><span class="Hyperlink">de Oliveira et al. (2013)</span></a> and <a href="#Tian-J--Zhao-Z--Zhang-L--Zhang-Q--Yu-Z--Li-J--Yang-R--2013-"><span class="Hyperlink">Tian et al. (2013)</span></a>. <a href="#Buchanan-FC--Van-Kessel-AG--Waldner-C--Christensen-D--Laarveld-B--Schmutz-SM--2003"><span class="Hyperlink">Buchanan et al. (2003)</span></a> and <a href="#Liefers-SC--te-Pas-MF--Veerkamp-RF--Chilliard-Y--Delavaud-C--Gerritsen-R--van-der-Lende-T--2003-"><span class="Hyperlink">Liefers et al. (2003)</span></a> have done research experiments to find out the role of leptin in milk production. Polymorphism in LEP gene of ovine has also been discussed (<a href="#Zhou-H--Hickford-JG--Gong-H--2009"><span class="Hyperlink">Zhou et al., 2009</span></a>) and its association with growth traits has been described by <a href="#Barzehkar-R--Salehi-A--Mahjoubi-F--2009-."><span class="Hyperlink">Barzehkar et al. (2009)</span></a>, <a href="#Tahmoorespur-M--Taheri-A--Valeh-MV--Saghi-DA--Ansari-M--2010-"><span class="Hyperlink">Tahmoorespur et al. (2010)</span></a>, <a href="#Shojaei-M--Abadi-MM--Fozi-MA--Dayani-O--Khezri-A--Akhondi-M--2011-.-Association-of-growth-trait-and"><span class="Hyperlink">Shojaei et al. (2011)</span></a>, and <a href="#Hajihosseinlo-A--Hashemi-A--Sadeghi-S--2012-."><span class="Hyperlink">Hajihosseinlo et al. (2012)</span></a>. In caprine, polymorphism in LEP gene has been reported by <a href="#Singh-SK--Rout-PK--Agarwal-R--Mandal-A--Singh-SK--Shukla-SN--Roy-R--2009-."><span class="Hyperlink">Singh et al. (2009)</span></a> and <a href="#Wang-PQ--Deng-LM--Zhang-YB--Chu-MX--Tan-Y--Fan-Q--Liu-CX--2011-"><span class="Hyperlink">Wang et al. (2011)</span></a>. Yet, association studies concerning markers in LEP gene have shown indecisive consequences. It could be said that the variations are due to alterations in environmental factors such as nutrition and genetic information of the animals, which are potential sources of genetic × environment relationship. Nutritional level, both in terms of quality and quantity of nutrients, becomes an imperative limitation in production systems that only depend on direct grazing of animals (<a href="#Corva-PM--Macedo-GVF--Soria-LA--Mazzucco-..-2009"><span class="Hyperlink">Corva et al., 2009</span></a>). Above described conclusions advocate that variation in LEP gene in domestic animals might be significant in fat deposition and feed intake, thus affecting growth and meat quality traits.</p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" xml:lang="en-GB">Role in growth</p>
		  <p class="Heading-1--Introduction----" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">Adipose tissue of a living body has a pertinent part in controlling the secretion of growth hormone (GH). GH and IGF-1, both intervene the fatness in individuals and their level is often reduced in fatty individuals (<a href="#Casabiell-X--Pi-eiro-V--Vega-F--de-la-Cruz-LF--Di-guez-C--Casanueva-FF--2001"><span class="Hyperlink">Casabiell et al., 2001</span></a>). Genetic alterations in LEP/ob gene or in their receptors (LEPR) alter the level of growth hormone in blood plasma (<a href="#Clement-K--Vaisse-C--Lahlou-N--Cabrol-S--Pelloux-V--Cassuto-D--Gourmelen-M--Dina-C--Chambaz-J--1998-"><span class="Hyperlink">Clement et al., 1998</span></a>). Growth hormone has a significant role in growth and development, as well as an important influence on composition of body and circulation of fats (<a href="#Wauters-M--Considine-RV--Van-Gaal-LF--2000-."><span class="Hyperlink">Wauters et al., 2000</span></a>).</p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text" xml:lang="en-GB">Moreover, structure of leptin is similar to that of GH and there exists likelihood of leptin binding to growth hormone binding proteins. LEPRs were recognized in arcuate and periventricular nuclei of hypothalamus (<a href="#Hashemi-A--Mardani-K--Farhadian-M--Ashrafi-I--Ranjbari-M--2011"><span class="Hyperlink">Hashemi et al., 2011</span></a>). In these hypothalamic nuclei, growth hormone and somatostatin releasing hormone neurons are also located. Though processes by which leptin mediate its actions are not entirely concluded, presence of LEPRs in nuclei of hypothalamus advocates the role of leptin at hypothalamus level. </p>
		  <p class="Body-Text" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text" xml:lang="en-GB">The hypophysis cerebri is the expression site of LEPR, where leptin mediate the release of growth hormone (<a href="#Shimon-I--Yan-X--Mago-n-DA--Friedman-TC--Melmed-S--1998-.-I"><span class="Hyperlink">Shimon et al., 1998</span></a>). The confirmation about involvement of leptin in the release of growth hormone was confirmed by intra-cerebro-ventricular (ICV) inoculation of leptin. The results showed that leptin antiserum administration to normal rats caused definite reduction in growth hormone levels in plasma. This study showed that different levels of leptin in body causes increase or decrease in GH secretion levels. Forty eight hours deprivation of food also decreased growth hormone production. When leptin was administered ICV, it showed the repressive eﬀect on growth hormone and growth hormone releasing hormone secretions (<a href="#Carro-E--Seoane-L--Senaris-R--Casanueva-C--Dieguez-C--2000"><span class="Hyperlink">Carro et al., 2000</span></a>). </p>
		  <p class="Body-Text" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">Leptin might be obligatory for typical development and growth of brain-endocrine (pituitary) system and has role in the expression of glial and neuronal proteins. This proposes that leptin might have a significant role in development (<a href="#Morash-B--Johnstone-L--Leopold-C--2000-"><span class="Hyperlink">Morash et al., 2000</span></a>). Leptin also seemed to be an important factor for growth of many cell types as pancreatic cells (<a href="#Tanabe-K--Okuya-S--Tanizawa-Y--Matsumoto-A--Oka-Y--1997-"><span class="Hyperlink">Tanabe et al., 1997</span></a>), white blood cells (<a href="#Lord-GM--Matarese-G--Howard-JK--Baker-JR--Bloom-SR--Lechler-LI--1998"><span class="Hyperlink">Lord et al., 1998</span></a>), and epithelial cells of trachea and squamous cells of lungs (<a href="#Tsuchiya-T--Shimizu-H--Horie-T--Mori-M--1999-."><span class="Hyperlink">Tsuchiya et al., 1999</span></a>).</p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" xml:lang="en-GB">Role in reproduction</p>
		  <p class="Heading-1--Introduction----" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">Sexual maturity in normal or obese animals is the result of maturation of the hypothalamic pituitary gonadal axis and its start is related to rise in gonadotropin releasing hormone action, which induces the release of sex steroid hormones and gonadotropins. This activation can be triggered by leptin which provokes the pituitary gland to release two hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH) (<a href="#Agarwal-R--Rout-PK--Singh-SK--2009-"><span class="Hyperlink">Agarwal et al., 2009</span></a>).</p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text" xml:lang="en-GB">There are some animals which are found hypogonadic because of mutation in LEP gene (<a href="#Strobel-A--Issad-T--Camoin-L--Ozata-M--Strosberg-AD--1998-"><span class="Hyperlink">Strobel et al., 1998</span></a>). Numerous research studies showed that leptin controls sexual maturity at hypothalamus level (<a href="#Casanueva--FF--Dieguez-C--1999"><span class="Hyperlink">Casanueva and Dieguez, 1999</span></a>; <a href="#Ehrhardt-RA--Bell-AW--Biosclair-YR--2002-."><span class="Hyperlink">Ehrhardt et al., 2002</span></a>; <a href="#Agarwal-R--Rout-PK--Singh-SK--2009-"><span class="Hyperlink">Agarwal et al., 2009</span></a>). Moreover the occurrence and involvement of LEPRs in hypothalamus with release of gonadotropic hormone confirms its role in sexual maturity or reproduction (<a href="#Magni-P--Vettor-R--Pagano-C--Calcagno-A--Beretta-E--Messi-E--Zanisi-M--Martini-L--Motta-M--1999-."><span class="Hyperlink">Magni et al., 1999</span></a>). </p>
		  <p class="Body-Text" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">In a research study on leptin treated macaques, mean levels and frequency of pulsatile secretion of FSH and LH in plasma varied significantly as compared to macaques on fast (<a href="#Finn-PD--Cunningham-MJ--Pau-KYF--Spies-HG--Clifton-DK--Steiner-RA--1998"><span class="Hyperlink">Finn et al., 1998</span></a>). Maternal leptin level influences LH secretion in young ones. The frequencies of LH pulsatile secretions were less in diet restricted lambs than the ones which were fed more leptin (<a href="#Morrison-CD--Daniel-JA--Holmberg-BJ--Djiane-J--Raver-N--Gertler-A--Keisler-DH--2001"><span class="Hyperlink">Morrison et al., 2001</span></a>). In feed-restricted cows and sheep, hypothalamic neuropeptide Y, inhibitor of secretion of luteinizing hormone in these species, was present in high amount (<a href="#Keisler-DH--Daniel-JA--Morrison-CD--1999-."><span class="Hyperlink">Keisler et al., 1999</span></a>). Subcutaneous administration of leptin induced the GH and LH secretion during fasting in estradiol-treated and castrated male sheep (<a href="#Nagatani-S--Zeng-Y--Keisler-DH--Foster-DL--Ja-e-CA--2000-"><span class="Hyperlink">Nagatani et al., 2000</span></a>). Intra-cerebro-ventricular administration of recombinant leptin in sheep caused a noticeable secretion of luteinizing hormone in cattle and <span class="CharOverride-8">in-vitro</span> researches confirm influence at the pituitary level. Low level of fertility related with malnourishment is a foremost interest for animal breeder. Under-nourished individuals will not attain sexual maturity unless they are well-nourished. Likewise, adult with normal estrous cycle will halt their cyclic activity when raised in under-nutrition conditions. These findings favor the assumptions of role of leptin as nutritive factor for reproductive physiology of animals. Isoforms of leptin receptor, together with long signaling form exist in gonadal tissues which indicate a direct endocrine activity of leptin on the gonads. On the other hand, local influence of leptin appears repressive for synthesis of steroids. <span class="CharOverride-8">In-vitro</span> researches revealed, leptin subdues ovarian production of estradiol and progesterone (<a href="#Karlsson-C--Lindell-K--Svensson-E--Bergh-C--Lind-P--Billig-H--1997"><span class="Hyperlink">Karlsson et al., 1997</span></a>).</p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">During gestation period levels of leptin in plasma are increased (<a href="#Stein-TP--Scholl-TO--Schluter-MD--Schroeder-CM--1998"><span class="Hyperlink">Stein et al., 1998</span></a>), higher level during second trimester (<a href="#Tamura-T--Goldenberg-R--Johnston-K--Cliver-S--1998-."><span class="Hyperlink">Tamura et al., 1998</span></a>), and decrease abruptly as parturition occurs. This decrease in leptin concentration during gestation happens with the incidence of circulating form of leptin, acting as a binding protein (<a href="#Lewandowski-K--Horn-R--O-Callaghan-CJ--Dunlop-D--Medley-GF--O-Hare-P--1999-"><span class="Hyperlink">Lewandowski et al., 1999</span></a>). Leptin production in placenta and developing fetus is also the cause of increased level of leptin in body. Involvement of synthesized leptin with growth of fetus or indication of energy status between dam and fetus is not much obvious (<a href="#Wauters-M--Considine-RV--Van-Gaal-LF--2000-."><span class="Hyperlink">Wauters et al., 2000</span></a>). The leptin receptor (long signaling and short transporting form) is also expressed by the placenta, signifying its role in development and growth of fetus (<a href="#Hoggard-N--Hunter-L--Trayhurn-P--Williams-P--Mercer-SW--1998-.-L"><span class="Hyperlink">Hoggard et al., 1998</span></a>). </p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">A significant amount of leptin is also produced by placenta of growing fetus and act as growth factor for fetus, signaling about the state of nutrition from the dam to her unborn (<a href="#Masuzaki-H--Ogawa-Y--Sagawa-N--1997-.-N"><span class="Hyperlink">Masuzaki et al., 1997</span></a>). The incidence of leptin was described in pre-implantated embryos as well. Leptin and its intra-cellular second messenger protein (STAT3) has been found in bovine embryos (<a href="#Boelhauve-M--Sinowatz-F-Wolf-E--Paula-Lopes-FF--2005"><span class="Hyperlink">Boelhauve et al., 2005</span></a>). This shows the significance of leptin in development of embryos and it will help researchers and scientists for improving implantation rates by conducting research studies on administration of exogenous leptin.</p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" xml:lang="en-GB">Role in milk production</p>
		  <p class="Heading-1--Introduction----" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">Leptin is considered as a potential candidate marker and has been found associated with milk yield and quality traits i.e. fat % and protein content of cattle milk. Association of different haplotypes of leptin (A59V/Sau3AI) have been found associated with fat, protein and milk yield in Polish Friesian black and white cattle (<a href="#Kulig-H.-2005."><span class="Hyperlink">Kulig, 2005</span></a>). Leptin is secreted in the mammary glands during lactation and it has also been found in the colostrum of cattle and other livestock species (<a href="#McFadin-EL--Morrison-CD--Buff-PR--Whitley-NC--Keisler-DH--2002-"><span class="Hyperlink">McFadin et al., 2002</span></a>). There are some propositions that leptin might has role in informing the CNS about energy/ fat reserves sufficient to support the energy demand of animal to ensure the successful lactation (<a href="#Casabiell-X--Pi-eiro-V--Vega-F--de-la-Cruz-LF--Di-guez-C--Casanueva-FF--2001"><span class="Hyperlink">Casabiell et al., 2001</span></a>). </p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" xml:lang="en-GB">Conclusion</p>
		  <p class="Heading-1--Introduction----" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">Many scientists have detected LEP gene polymorphism in bovines, caprines, ovines and swines. They have also found significant associations of LEP gene variation with various productive and reproductive traits. Current genetic improvement schemes can be enhanced by using these research studies which might take part in increasing the productivity in our indigenous animals. The prospect to change the body composition by management or selection can assist the livestock farmers to produce meat that likely fulfils the expectations of consumers. The research findings could be indicative of other important traits in animals, yet more research work is obligatory to validate the results before their implication in marker-assisted selection (MAS).</p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" xml:lang="en-GB">Future perspectives</p>
		  <p class="Heading-1--Introduction----" xml:lang="en-GB">&nbsp;</p>
			<p class="Body-Text ParaOverride-1" xml:lang="en-GB">Leptin has important role in regulating many productive and reproductive traits. It has been studied in various animals like cattle, buffalo, sheep, goat and pigs in Brazil, Egypt, India, Iran, Italy and Romania, to name a few. There is very less work done on leptin in Pakistan thus it would be pertinent to characterize and find single nucleotide polymorphism in LEP gene in our indigenous breeds and also its relationship with numerous productive and reproductive traits. The amount of circulating leptin would be a sign of fat contents present in live animals. This would enable the farmers to develop more suitable strategies for fattening and milking management, thus increasing the easy sale of animals to market. Still, a lot of research work is required in this regard.</p>
		  <p class="Body-Text ParaOverride-1" xml:lang="en-GB">&nbsp;</p>
			<p class="Heading-1--Introduction----" xml:lang="en-GB">References</p>
		  <p class="Heading-1--Introduction----" xml:lang="en-GB">&nbsp;</p>
			
			  <li class="References ParaOverride-2"><a id="Agarwal-R--Rout-PK--Singh-SK--2009-"></a>Agarwal R, Rout PK, Singh SK (2009). Leptin: A biomolecule for enhancing livestock productivity. Indian J. Biotechnol. 8(2): 169-176.</li>
				<li class="References ParaOverride-2"><a id="Ahima-RS--Prabakaran-D--Mantzoros-C--Qu-D--Lowell-B--Maratos-Flier-E--Flier-JS--1996"></a>Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS (1996). Role of leptin in the neuroendocrine response to fasting. Nature. 382: 250-252. <a href="http://dx.doi.org/10.1038/382250a0 "><span class="Hyperlink">http://dx.doi.org/10.1038/382250a0 </span></a>PMid:8717038</li>
				<li class="References ParaOverride-2"><a id="Barb-CR--Kraeling-RR--2004"></a>Barb CR, Kraeling RR (2004). Role of leptin in the regulation of gonadotropin secretion in farm animals. Anim. Reprod. Sci. 82-83: 155-167. <a href="http://dx.doi.org/10.1016/j.anireprosci.2004.04.032"><span class="Hyperlink">http://dx.doi.org/10.1016/j.anireprosci.2004.04.032</span></a> PMid:15271450</li>
				<li class="References ParaOverride-2"><a id="Barzehkar-R--Salehi-A--Mahjoubi-F--2009-."></a>Barzehkar R, Salehi A, Mahjoubi F (2009). Polymorphisms of the ovine leptin gene and its association with growth and carcass traits in three Iranian sheep breeds. Iran. J. Biotechnol. 7(4): 241-246.</li>
				<li class="References ParaOverride-2"><a id="Boelhauve-M--Sinowatz-F-Wolf-E--Paula-Lopes-FF--2005"></a>Boelhauve M, Sinowatz F,Wolf E, Paula-Lopes FF (2005). Maturation of bovine oocytes in the presence of leptin improves development and reduces apoptosis of <span class="CharOverride-8">in vitro</span>-produced blastocysts. Bio. Reprod. 73(4): 737–744. <a href="http://dx.doi.org/10.1095/biolreprod.105.041103"><span class="Hyperlink">http://dx.doi.org/10.1095/biolreprod.105.041103</span></a> PMid:15958729</li>
				<li class="References ParaOverride-2"><a id="Boucher-D--Palin-MF--Castonguay-F--Gari-py-C--Pothier-F--2006"></a>Boucher D, Palin MF, Castonguay F, Gariépy C, Pothier F (2006). Detection of polymorphisms in the ovine leptin (LEP) gene: Association of a single nucleotide polymorphism with muscle growth and meat quality traits. Can. J. Anim. Sci. 86(1): 31-35.</li>
				<li class="References ParaOverride-2"><a id="Buchanan-FC--Van-Kessel-AG--Waldner-C--Christensen-D--Laarveld-B--Schmutz-SM--2003"></a>Buchanan FC, Van Kessel AG, Waldner C, Christensen D, Laarveld B, Schmutz SM (2003). An association between a leptin single nucleotide polymorphism and milk and protein yield. J. Dairy Sci. 86(10): 3164-3166. <a href="http://dx.doi.org/10.3168/jds.S0022-0302(03)73918-6"><span class="Hyperlink">http://dx.doi.org/10.3168/jds.S0022-0302(03)73918-6</span></a></li>
				<li class="References ParaOverride-2"><a id="Carro-E--Seoane-L--Senaris-R--Casanueva-C--Dieguez-C--2000"></a>Carro E, Seoane L, Senaris R, Casanueva C, Dieguez C (2000). Leptin increases in vivo GH responses to GHRH and GHRP-6 in food-deprived rats. Eur. J. Endocrinol. 142(1): 66-70. <a href="http://dx.doi.org/10.1530/eje.0.1420066"><span class="Hyperlink">http://dx.doi.org/10.1530/eje.0.1420066</span></a></li>
				<li class="References ParaOverride-2"><a id="Casabiell-X--Pi-eiro-V--Vega-F--de-la-Cruz-LF--Di-guez-C--Casanueva-FF--2001"></a>Casabiell X, Pi-eiro V, Vega F, de la Cruz LF, Diéguez C, Casanueva FF (2001). Leptin, reproduction and sex steroids. Pituitary. 4(1-2): 93-99. <a href="http://dx.doi.org/10.1023/A:1012999130035"><span class="Hyperlink">http://dx.doi.org/10.1023/A:1012999130035</span></a> PMid:11824514</li>
				<li class="References ParaOverride-2"><a id="Casanueva--FF--Dieguez-C--1999"></a>Casanueva, FF, Dieguez C (1999). Neuroendocrine regulation and actions of leptin. Front. Neuroendocrinol. 20(<span class="CharOverride-13">4</span>): 317-363. <a href="http://dx.doi.org/10.1006/frne.1999.0187"><span class="Hyperlink">http://dx.doi.org/10.1006/frne.1999.0187</span></a> PMid:10569281</li>
				<li class="References ParaOverride-2"><a id="Chung-ER--Shin-SC--Shin-KH--Chung-KY--2008"></a>Chung ER, Shin SC, Shin KH, Chung KY (2008). SNP discovery in the leptin promoter gene and association with meat quality and carcass traits in Korean cattle. Asian-australas J. Anim. Sci. 21(12): 1689-1695. <a href="http://dx.doi.org/10.5713/ajas.2008.80112"><span class="Hyperlink">http://dx.doi.org/10.5713/ajas.2008.80112</span></a></li>
				<li class="References ParaOverride-2"><a id="Clement-K--Vaisse-C--Lahlou-N--Cabrol-S--Pelloux-V--Cassuto-D--Gourmelen-M--Dina-C--Chambaz-J--1998-"></a>Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 392: 398-401. <a href="http://dx.doi.org/10.1038/32911"><span class="Hyperlink">http://dx.doi.org/10.1038/32911</span></a> PMid:9537324</li>
				<li class="References ParaOverride-2"><a id="Corva-PM--Macedo-GVF--Soria-LA--Mazzucco-..-2009"></a>Corva PM, Macedo GVF, Soria LA, Mazzucco JP, Motter M, Villarreal EL, Schor A, Mezzadra CA, Melucci LM, Miquel MC (2009). Effect of leptin gene polymorphisms on growth, slaughter and meat quality traits of grazing Brangus steers. Genet. Mol. Res. 8(1): 105-116. <a href="http://dx.doi.org/10.4238/vol8-1gmr556"><span class="Hyperlink">http://dx.doi.org/10.4238/vol8-1gmr556</span></a> PMid:19283678</li>
				<li class="References ParaOverride-2"><a id="de-Oliveira-JA--Cunha-CMD--Crispim-BDA--Seno-LDO--Fernandes-ARM--Nogueira-GDP--Grisolia-AB--2013"></a>de Oliveira JA, Cunha CMD, Crispim BDA, Seno LDO, Fernandes ARM, Nogueira GDP, Grisolia AB (2013). Association of the leptin gene with carcass characteristics in Nellore cattle. Anim. Biotechnol. 24(3): 229-242. <a href="http://dx.doi.org/10.1080/10495398.2013.770008"><span class="Hyperlink">http://dx.doi.org/10.1080/10495398.2013.770008</span></a> PMid:23777351</li>
				<li class="References ParaOverride-2"><a id="Ehrhardt-RA--Bell-AW--Biosclair-YR--2002-."></a>Ehrhardt RA, Bell AW, Biosclair YR (2002). Spatial and development regulation of leptin in fetal sheep. Pysiol. Regul. Integr. Comp. Physiol. 282(6): 1628-1635.</li>
				<li class="References ParaOverride-2"><a id="Finn-PD--Cunningham-MJ--Pau-KYF--Spies-HG--Clifton-DK--Steiner-RA--1998"></a>Finn PD, Cunningham MJ, Pau KYF, Spies HG, Clifton DK, Steiner RA (1998). The stimulatory eﬀect of leptin on the neuroendocrine reproductive axis of the monkey. Endocrinol. 139(11): 4652-4662. <a href="http://dx.doi.org/10.1210/endo.139.11.6297"><span class="Hyperlink">http://dx.doi.org/10.1210/endo.139.11.6297</span></a> <a href="http://dx.doi.org/10.1210/en.139.11.4652"><span class="Hyperlink">http://dx.doi.org/10.1210/en.139.11.4652</span></a> PMid:9794477</li>
				<li class="References ParaOverride-2"><a id="Frank-S--Stallmeyer-B--Kampfer-H--Kolb-N--Pfeilschifter-J--2000-"></a>Frank S, Stallmeyer B, Kampfer H, Kolb N, Pfeilschifter J (2000). Leptin enhances woung re-epithelialization and constitutes a direct function of leptin in skin repair. J. Clin. Invest. 106(4): 501-509. <a href="http://dx.doi.org/10.1172/JCI9148"><span class="Hyperlink">http://dx.doi.org/10.1172/JCI9148</span></a> PMid:10953025 PMCid:PMC380250</li>
				<li class="References ParaOverride-2"><a id="Geary-TW--McFadin-EL--MacNeil-MD--Grings-EF--Short-RR--Funston-RN--Keisler-DH--2003-."></a>Geary TW, McFadin EL, MacNeil MD, Grings EF, Short RR, Funston RN, Keisler DH (2003). Leptin as a predictor of carcass composition in beef cattle. J. Anim. Sci. 81(1): 1-8. PMid:12597366</li>
				<li class="References ParaOverride-2"><a id="Guo-Y--Chen-H--Lan-X--Zhang-B--Pan-C--Zhang-L--Zhang-C--Zhao-M--2008-."></a>Guo Y, Chen H, Lan X, Zhang B, Pan C, Zhang L, Zhang C, Zhao M (2008). Novel SNPs of the bovine LEPR gene and their association with growth traits. Biochem. Genet. 46(11-12): 828-834. <a href="http://dx.doi.org/10.1007/s10528-008-9197-z"><span class="Hyperlink">http://dx.doi.org/10.1007/s10528-008-9197-z</span></a> PMid:18807168</li>
				<li class="References ParaOverride-2"><a id="Hafez-YM--2013"></a>Hafez YM (2013). Effect of climatic conditions on blood plasma IgG and leptin profiles in buffaloes. Egyptian J. Anim. Prod. 50(1): 1-6.</li>
				<li class="References ParaOverride-2"><a id="Hajihosseinlo-A--Hashemi-A--Sadeghi-S--2012-."></a>Hajihosseinlo A, Hashemi A, Sadeghi S (2012). Association between polymorphism in exon 3 of leptin gene and growth traits in the Makooei sheep of Iran. Livest. Res. Rural. Dev. 24(166). Available from: <a href="http://www.lrrd.org/lrrd24/9/haji24166.htm"><span class="Hyperlink">http://www.lrrd.org/lrrd24/9/haji24166.htm</span></a>.</li>
				<li class="References ParaOverride-2"><a id="Hashemi-A--Mardani-K--Farhadian-M--Ashrafi-I--Ranjbari-M--2011"></a>Hashemi A, Mardani K, Farhadian M, Ashrafi I, Ranjbari M (2011). Allelic polymorphism of Makoei sheep leptin gene identified by polymerase chain reaction and single strand conformation polymorphism. Afr. J. Biotechnol. 10(77): 17903-17906.</li>
				<li class="References ParaOverride-2"><a id="Hoggard-N--Hunter-L--Trayhurn-P--Williams-P--Mercer-SW--1998-.-L"></a>Hoggard N, Hunter L, Trayhurn P, Williams P, Mercer SW (1998). Leptin and reproduction. Proc. Nutr. Soc. 57: 421-427. <a href="http://dx.doi.org/10.1079/PNS19980061"><span class="Hyperlink">http://dx.doi.org/10.1079/PNS19980061</span></a> PMid:9794000</li>
				<li class="References ParaOverride-2"><a id="Hossner-KL--McCusker-RH--Dodson-MV--1997-."></a>Hossner KL, McCusker RH, Dodson MV (1997). Insulin-like growth factors and their binding proteins in domestic animals. Anim. Sci. 64(1): 1-15. <a href="http://dx.doi.org/10.1017/S1357729800015502"><span class="Hyperlink">http://dx.doi.org/10.1017/S1357729800015502</span></a></li>
				<li class="References ParaOverride-2"><a id="Hossner-KL.-1998"></a>Hossner KL (1998). Cellular, molecular and physiological aspects of leptin: Potential application in animal production. Can. J. Anim. Sci. 78(4): 463-472. <a href="http://dx.doi.org/10.4141/A98-061"><span class="Hyperlink">http://dx.doi.org/10.4141/A98-061</span></a></li>
				<li class="References ParaOverride-2"><a id="Houseknecht-KL--Baile-CA--Matteri-RL--Spurlock-ME--1998"></a>Houseknecht KL, Baile CA, Matteri RL, Spurlock ME (1998). The biology of leptin. a review. J. Anim. Sci. 76(5): 1405-1420. PMid:9621947</li>
				<li class="References ParaOverride-2"><a id="Javanmard-A--Mohammadabadi-M--Zarrigabayi-G--Gharahedaghi-A--Nassiry-M--Javadmansh-A--Asadzadeh-N--2"></a>Javanmard A, Mohammadabadi M, Zarrigabayi G, Gharahedaghi A, Nassiry M, Javadmansh A, Asadzadeh N (2008). Polymorphism within the intron region of the bovine leptin gene in Iranian Sarabi cattle (Iranian Bos taurus). Russ. J. Genet. 44(4): 495-497.<a href="http://dx.doi.org/10.1134/S1022795408040169"><span class="Hyperlink">http://dx.doi.org/10.1134/S1022795408040169</span></a></li>
				<li class="References ParaOverride-2"><a id="Karlsson-C--Lindell-K--Svensson-E--Bergh-C--Lind-P--Billig-H--1997"></a>Karlsson C, Lindell K, Svensson E, Bergh C, Lind P, Billig H (1997). Expression of functional leptin receptors in the human ovary. J. Clin. Endocrinol. Metab. 82(12): 4144-4148. <a href="http://dx.doi.org/10.1210/jcem.82.12.4446"><span class="Hyperlink">http://dx.doi.org/10.1210/jcem.82.12.4446</span></a> <a href="http://dx.doi.org/10.1210/jc.82.12.4144"><span class="Hyperlink">http://dx.doi.org/10.1210/jc.82.12.4144</span></a> PMid:9398729</li>
				<li class="References ParaOverride-2"><a id="Keisler-DH--Daniel-JA--Morrison-CD--1999-."></a>Keisler DH, Daniel JA, Morrison CD (1999). The role of leptin in nutritional status and reproductive function. J. Reprod. Fertil. Suppl. 54: 425-435. PMid:10692873</li>
				<li class="References ParaOverride-2"><a id="Kennedy-GC--1953-."></a>Kennedy GC (1953). The role of depot fat in the hypothalamic control of food intake in the rat. Proc. R. Soc. Lond., B, Biol. Sci. 140: 578-592. <a href="http://dx.doi.org/10.1098/rspb.1953.0009"><span class="Hyperlink">http://dx.doi.org/10.1098/rspb.1953.0009</span></a> PMid:13027283</li>
				<li class="References ParaOverride-2"><a id="Kulig-H--Kmie--M--2009-"></a>Kulig H, Kmieć M (2009). Association between leptin gene polymorphisms and growth traits in Limousin cattle. Russ. J. Genet. 45(6): 738-741. <a href="http://dx.doi.org/10.1134/S1022795409060131"><span class="Hyperlink">http://dx.doi.org/10.1134/S1022795409060131</span></a></li>
				<li class="References ParaOverride-2"><a id="Kulig-H--Kmie--M--Kowalewska-Luczak-I--Andziak-G--2009-"></a>Kulig H, Kmieć M, Kowalewska-Luczak I, Andziak G (2009). Effect of leptin gene polymorphisms on milk production traits of Jersey cows. Turk. J. Vet. Anim. Sci. 33(2): 143-146</li>
				<li class="References ParaOverride-2"><a id="Kulig-H.-2005."></a>Kulig H. 2005. Association between leptin combined genotypes and milk performance traits of Polish Black-and-White cows. Arch. Tierz. 48: 547-554.</li>
				<li class="References ParaOverride-2"><a id="Lagonigro-R--Wiener-P--Pilla-F--Woolliams-JA--Williams-JL--2003-"></a>Lagonigro R, Wiener P, Pilla F, Woolliams JA, Williams JL (2003). A new mutation in the coding region of the bovine leptin gene associated with feed intake. Anim Genet. 34(5): 371-374. <a href="http://dx.doi.org/10.1046/j.1365-2052.2003.01028.x"><span class="Hyperlink">http://dx.doi.org/10.1046/j.1365-2052.2003.01028.x</span></a> PMid:14510674</li>
				<li class="References ParaOverride-2"><a id="Lewandowski-K--Horn-R--O-Callaghan-CJ--Dunlop-D--Medley-GF--O-Hare-P--1999-"></a>Lewandowski K, Horn R, O’Callaghan CJ, Dunlop D, Medley GF, O’Hare P (1999). Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies. J. Clin. Endocrinol. Metab. 84(1): 300-306. <a href="http://dx.doi.org/10.1210/jcem.84.1.5401"><span class="Hyperlink">http://dx.doi.org/10.1210/jcem.84.1.5401</span></a> PMid:9920099</li>
				<li class="References ParaOverride-2"><a id="Liefers-SC--te-Pas-MF--Veerkamp-RF--Chilliard-Y--Delavaud-C--Gerritsen-R--van-der-Lende-T--2003-"></a>Liefers SC, te Pas MF, Veerkamp RF, Chilliard Y, Delavaud C, Gerritsen R, van der Lende T (2003). Association of leptin gene polymorphisms with serum leptin concentration in dairy cows. Mamm. Genome. 14(9): 657-663. <a href="http://dx.doi.org/10.1007/s00335-003-2275-y"><span class="Hyperlink">http://dx.doi.org/10.1007/s00335-003-2275-y</span></a> PMid:14629116</li>
				<li class="References ParaOverride-2"><a id="Lord-GM--Matarese-G--Howard-JK--Baker-JR--Bloom-SR--Lechler-LI--1998"></a>Lord GM, Matarese G, Howard JK, Baker JR, Bloom SR, Lechler LI (1998). Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 394: 897-901. <a href="http://dx.doi.org/10.1038/29795"><span class="Hyperlink">http://dx.doi.org/10.1038/29795</span></a> PMid:9732873</li>
				<li class="References ParaOverride-2"><a id="Lusk-JL--2007-"></a>Lusk JL (2007). Association of single nucleotide polymorphisms in the leptin gene with bodyweight and backfat growth curve parameters for beef cattle. J. Anim. Sci. 85(5): 1865-1872. <a href="http://dx.doi.org/10.2527/jas.2006-665 "><span class="Hyperlink">http://dx.doi.org/10.2527/jas.2006-665</span></a><span class="Hyperlink"> </span>PMid:17431048</li>
				<li class="References ParaOverride-2"><a id="Magni-P--Vettor-R--Pagano-C--Calcagno-A--Beretta-E--Messi-E--Zanisi-M--Martini-L--Motta-M--1999-."></a>Magni P, Vettor R, Pagano C, Calcagno A, Beretta E, Messi E, Zanisi M, Martini L, Motta M (1999). Expression of a leptin receptor in immortalized gonadotropin-releasing hormone-secreting neurons. Endocrinol. 140(4): 1581-1585. <a href="http://dx.doi.org/10.1210/endo.140.4.6622"><span class="Hyperlink">http://dx.doi.org/10.1210/endo.140.4.6622</span></a> <a href="http://dx.doi.org/10.1210/en.140.4.1581 "><span class="Hyperlink">http://dx.doi.org/10.1210/en.140.4.1581</span></a><span class="Hyperlink"> </span>PMid:10098491</li>
				<li class="References ParaOverride-2"><a id="Masuzaki-H--Ogawa-Y--Sagawa-N--1997-.-N"></a><a id="Masuzaki-H--Ogawa-Y--Sagawa-N--1997-.-N-1"></a>Masuzaki H, Ogawa Y, Sagawa N (1997). Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat. Med. 3(9): 1029-1033. <a href="http://dx.doi.org/10.1038/nm0997-1029"><span class="Hyperlink">http://dx.doi.org/10.1038/nm0997-1029</span></a> PMid:9288733</li>
				<li class="References ParaOverride-2"><a id="McFadin-EL--Morrison-CD--Buff-PR--Whitley-NC--Keisler-DH--2002-"></a>McFadin EL, Morrison CD, Buff PR, Whitley NC, Keisler DH (2002). Leptin concentrations in periparturient ewes and their subsequent offspring. J. Anim. Sci. 80(3): 738-743 PMid:11890410</li>
				<li class="References ParaOverride-2"><a id="Morash-B--Johnstone-L--Leopold-C--2000-"></a>Morash B, Johnstone L, Leopold C (2000). The regulation of leptin gene expression in the C6 glioblastoma cell line. Mol. Cell. Endocrinol. 165(1): 97-105. <a href="http://dx.doi.org/10.1016/S0303-7207(00)00259-8"><span class="Hyperlink">http://dx.doi.org/10.1016/S0303-7207(00)00259-8</span></a></li>
				<li class="References ParaOverride-2"><a id="Morrison-CD--Daniel-JA--Holmberg-BJ--Djiane-J--Raver-N--Gertler-A--Keisler-DH--2001"></a>Morrison CD, Daniel JA, Holmberg BJ, Djiane J, Raver N, Gertler A, Keisler DH (2001). Central infusion of leptin into well-fed and undernourished ewe lambs: eﬀects on feed intake and serum concentrations of growth hormone and luteinizing hormone. J. Endocrinol. 168(2): 317-324. <a href="http://dx.doi.org/10.1677/joe.0.1680317"><span class="Hyperlink">http://dx.doi.org/10.1677/joe.0.1680317</span></a> PMid:11182769</li>
				<li class="References ParaOverride-2"><a id="Nagatani-S--Zeng-Y--Keisler-DH--Foster-DL--Ja-e-CA--2000-"></a>Nagatani S, Zeng Y, Keisler DH, Foster DL, Jaﬀe CA (2000) Leptin regulates pulsatile luteinizing hormone and growth hormone secretion in the sheep. Endocrinol. 141(11): 3965-3975. <a href="http://dx.doi.org/10.1210/endo.141.11.7762"><span class="Hyperlink">http://dx.doi.org/10.1210/endo.141.11.7762</span></a> <a href="http://dx.doi.org/10.1210/en.141.11.3965 "><span class="Hyperlink">http://dx.doi.org/10.1210/en.141.11.3965</span></a></li>
				<li class="References ParaOverride-2"><a id="Nassiri-MR--Moussavi-AH--Alshawkany-A--Roudsari-SG--2007-."></a>Nassiri MR, Moussavi AH, Alshawkany A, Roudsari SG (2007). Leptin gene polymorphism in Iranian native Golpayegani and Taleshi cows. Pak. J. Biol. Sci. 10: 3738-3741. <a href="http://dx.doi.org/10.3923/pjbs.2007.3738.3741"><span class="Hyperlink">http://dx.doi.org/10.3923/pjbs.2007.3738.3741</span></a></li>
				<li class="References ParaOverride-2"><a id="Nkrumah-JD--Li-C--Yu-J--Hansen-C--Keisler-DH--Moore-SS--2005-"></a>Nkrumah JD, Li C, Yu J, Hansen C, Keisler DH, Moore SS (2005). Polymorphisms in the bovine leptin promoter associated with serum leptin concentration, growth, feed intake, feeding behavior, and measures of carcass merit. J. Anim. Sci. 83(1): 20-28. PMid:15583038</li>
				<li class="References ParaOverride-2"><a id="Olusi-S--Al-Awadhi-A--Abiaka-C--Abraham-M--George-S--2003-"></a>Olusi S, Al-Awadhi A, Abiaka C, Abraham M, George S (2003). Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population. Biol. Trace Elem. Res. 91(2): 137-144. <a href="http://dx.doi.org/10.1385/BTER:91:2:137"><span class="Hyperlink">http://dx.doi.org/10.1385/BTER:91:2:137</span></a></li>
				<li class="References ParaOverride-2"><span class="Hyperlink"><a id="Pomp-D--Zou-T--Clutter-AC--Barendse-W--1997-."></a></span>Pomp D, Zou T, Clutter AC, Barendse W (1997). Rapid communication: mapping of leptin to bovine chromosome 4 by linkage analysis of a PCR-based polymorphism. J. Anim. Sci. 75(5): 1427-1427.</li>
				<li class="References ParaOverride-2"><a id="Schenkel-FS--Miller-SP--Ye-X--Moore-SS--Nkrumah-JD--Li-C--Yu-J--Mandell-IB--Wilton-JW--Williams-JL--"></a>Schenkel FS, Miller SP, Ye X, Moore SS, Nkrumah JD, Li C, Yu J, Mandell IB, Wilton JW, Williams JL (2005). Association of single nucleotide polymorphisms in the leptin gene with carcass and meat quality traits of beef cattle. J. Anim. Sci. 83(9): 2009-2020. PMid:16100055</li>
				<li class="References ParaOverride-2"><a id="Shimon-I--Yan-X--Mago-n-DA--Friedman-TC--Melmed-S--1998-.-I"></a>Shimon I, Yan X, Magoﬃn DA, Friedman TC, Melmed S (1998). Intact leptin receptor is selectively expressed in human fetal pituitary and pituitary adenomas and signals human fetal pituitary growth hormone secretion. J. Clin. Endocrinol. Metab. 83(11): 4059-4064. <a href="http://dx.doi.org/10.1210/jcem.83.11.5273"><span class="Hyperlink">http://dx.doi.org/10.1210/jcem.83.11.5273</span></a> <a href="http://dx.doi.org/10.1210/jc.83.11.4059"><span class="Hyperlink">http://dx.doi.org/10.1210/jc.83.11.4059</span></a> PMid:9814492</li>
				<li class="References ParaOverride-2"><a id="Shin-SC--Chung-ER--2007-.-Association-of-SNP-marker-in-the-leptin-gene-w"></a>Shin SC, Chung ER (2007). Association of SNP marker in the leptin gene with carcass and meat quality traits in Korean cattle. Asian-australas J. Anim. Sci. 20(1): 1-6. <a href="http://dx.doi.org/10.5713/ajas.2007.1"><span class="Hyperlink">http://dx.doi.org/10.5713/ajas.2007.1</span></a></li>
				<li class="References ParaOverride-2"><a id="Shojaei-M--Abadi-MM--Fozi-MA--Dayani-O--Khezri-A--Akhondi-M--2011-.-Association-of-growth-trait-and"></a>Shojaei M, Abadi MM, Fozi MA, Dayani O, Khezri A, Akhondi M (2011). Association of growth trait and Leptin gene polymorphism in Kermani sheep. J. Cell Mol. Res. 2(1): 67-73.</li>
				<li class="References ParaOverride-2"><a id="Singh-SK--Rout-PK--Agarwal-R--Mandal-A--Singh-SK--Shukla-SN--Roy-R--2009-."></a>Singh SK, Rout PK, Agarwal R, Mandal A, Singh SK, Shukla SN, Roy R (2009). Characterization of exon 2 &amp; intron 2 of leptin gene in Indian goats. Anim. Biotechnol. 20(2): 80-85. <a href="http://dx.doi.org/10.1080/10495390902823885"><span class="Hyperlink">http://dx.doi.org/10.1080/10495390902823885</span></a> PMid:19370458 </li>
				<li class="References ParaOverride-2"><a id="Sinha-MK--Opentanova-I--Ohannesian-JP--Kolaczynski-JW--Heiman-ML--Hale-J--Becker-GW--Bowsher-RR--Ste"></a>Sinha MK, Opentanova I, Ohannesian JP, Kolaczynski JW, Heiman ML, Hale J, Becker GW, Bowsher RR, Stephens TW, Caro JF (1996). Evidence of free and bound leptin in human circulation – studies in lean and obese subjects and during short-term fasting. J. Clin. Invest. 98(6): 1277-1282. <a href="http://dx.doi.org/10.1172/JCI118913"><span class="Hyperlink">http://dx.doi.org/10.1172/JCI118913</span></a><span class="CharOverride-14"> </span>PMid:8823291 PMCid:PMC507552 </li>
				<li class="References ParaOverride-2"><a id="Stein-TP--Scholl-TO--Schluter-MD--Schroeder-CM--1998"></a>Stein TP, Scholl TO, Schluter MD, Schroeder CM (1998). Plasma leptin inﬂuences gestational weight gain and postpartum weight retention. Am. J. Clin. Nutr. 68(6): 1236-1240. PMid:9846852</li>
				<li class="References ParaOverride-2"><a id="Strobel-A--Issad-T--Camoin-L--Ozata-M--Strosberg-AD--1998-"></a>Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD (1998). A leptin missense mutation associated with hypogonadism and morbid obesity. Nat. Genet. 18(3): 213-215. <a href="http://dx.doi.org/10.1038/ng0398-213"><span class="Hyperlink">http://dx.doi.org/10.1038/ng0398-213</span></a> PMid:9500540</li>
				<li class="References ParaOverride-2"><a id="Tahmoorespur-M--Taheri-A--Valeh-MV--Saghi-DA--Ansari-M--2010-"></a>Tahmoorespur M, Taheri A, Valeh MV, Saghi DA, Ansari M (2010). Effect of Leptin and ghrelin gene polymorphisms on estimated breeding values of growth traits in Baluchi sheep. 14th AAAP Animal Science Congress. PMid:20852099 </li>
				<li class="References ParaOverride-2"><a id="Tamura-T--Goldenberg-R--Johnston-K--Cliver-S--1998-."></a>Tamura T, Goldenberg R, Johnston K, Cliver S (1998). Serum leptin concentrations during pregnancy and their relationship to fetal growth. Obstet. Gynecol. 91(3): 389-395. <a href="http://dx.doi.org/10.1016/S0029-7844(97)00670-4"><span class="Hyperlink">http://dx.doi.org/10.1016/S0029-7844(97)00670-4</span></a></li>
				<li class="References ParaOverride-2"><a id="Tanabe-K--Okuya-S--Tanizawa-Y--Matsumoto-A--Oka-Y--1997-"></a>Tanabe K, Okuya S, Tanizawa Y, Matsumoto A, Oka Y (1997). Leptin induces proliferation of pancreatic b-cell line MIN6 through activation of mitogen-activated protein kinase. Biochem. Biophys. Res. Commun. 241(3): 765-768. <a href="http://dx.doi.org/10.1006/bbrc.1997.7894"><span class="Hyperlink">http://dx.doi.org/10.1006/bbrc.1997.7894</span></a> PMid:9434783 </li>
				<li class="References ParaOverride-2"><a id="Tian-J--Zhao-Z--Zhang-L--Zhang-Q--Yu-Z--Li-J--Yang-R--2013-"></a>Tian J, Zhao Z, Zhang L, Zhang Q, Yu Z, Li J, Yang R (2013). Association of the leptin gene E2-169T&gt; C and E3-299T&gt; A mutations with carcass and meat quality traits of the Chinese Simmental-cross steers. Gene. 518(2): 443-448. <a href="http://dx.doi.org/10.1016/j.gene.2012.11.071"><span class="Hyperlink">http://dx.doi.org/10.1016/j.gene.2012.11.071</span></a> PMid:23291417 </li>
				<li class="References ParaOverride-2"><a id="Tsuchiya-T--Shimizu-H--Horie-T--Mori-M--1999-."></a>Tsuchiya T, Shimizu H, Horie T, Mori M (1999). Expression of leptin receptor in lung: leptin as a growth factor. Eur. J. Pharmacol. 365(2): 273-279. <a href="http://dx.doi.org/10.1016/S0014-2999(98)00884-X "><span class="Hyperlink">http://dx.doi.org/10.1016/S0014-2999(98)00884-X</span></a><span class="Hyperlink"> </span></li>
				<li class="References ParaOverride-2"><a id="Van-der-Lende-T--te-Pas-MF--Veerkamp-R--Liefers-S--2005-."></a>Van der Lende T, te Pas MF, Veerkamp R, Liefers S (2005). Leptin gene polymorphisms and their phenotypic associations. Vitam. Horm. 71: 373-404. <a href="http://dx.doi.org/10.1016/S0083-6729(05)71013-X"><span class="Hyperlink">http://dx.doi.org/10.1016/S0083-6729(05)71013-X</span></a></li>
				<li class="References ParaOverride-2"><a id="Wang-PQ--Deng-LM--Zhang-YB--Chu-MX--Tan-Y--Fan-Q--Liu-CX--2011-"></a>Wang PQ, Deng LM, Zhang YB, Chu MX, Tan Y, Fan Q, Liu CX (2011). Identification of polymorphism on leptin receptor gene of goats in southwest China. Small Rumin. Res. 96(2-3): 120-125. <a href="http://dx.doi.org/10.1016/j.smallrumres.2011.01.016"><span class="Hyperlink">http://dx.doi.org/10.1016/j.smallrumres.2011.01.016</span></a></li>
				<li class="References ParaOverride-2"><a id="Wauters-M--Considine-RV--Van-Gaal-LF--2000-."></a>Wauters M, Considine RV, Van Gaal LF (2000). Human leptin: from an adipocyte hormone to an endocrine mediator. Eur. J. Endocrinol. 143(3): 293-311. <a href="http://dx.doi.org/10.1530/eje.0.1430293 "><span class="Hyperlink">http://dx.doi.org/10.1530/eje.0.1430293</span></a><span class="Hyperlink"> </span>PMid:11022169</li>
				<li class="References ParaOverride-2"><a id="Yang-D--Chen-H--Wang-X--Tian-Z--Tang-L--Zhang-Z--Lei-C--Zhang-L--Wang-Y--2007-"></a>Yang D, Chen H, Wang X, Tian Z, Tang L, Zhang Z, Lei C, Zhang L, Wang Y (2007). Association of polymorphisms of leptin gene with body weight and body sizes indexes in Chinese indigenous cattle. J. Genet. Genomics. 34(5): 400-405. <a href="http://dx.doi.org/10.1016/S1673-8527(07)60043-5"><span class="Hyperlink">http://dx.doi.org/10.1016/S1673-8527(07)60043-5</span></a></li>
				<li class="References ParaOverride-2"><a id="Zhou-H--Hickford-JG--Gong-H--2009"></a>Zhou H, Hickford JG, Gong H (2009). Identification of allelic polymorphism in the ovine leptin gene. Mol. Biotechnol. 41(1): 22-25. <a href="http://dx.doi.org/10.1007/s12033-008-9090-3 "><span class="Hyperlink">http://dx.doi.org/10.1007/s12033-008-9090-3</span></a><span class="Hyperlink"> </span>PMid:18636347</li>
			
			<p>&nbsp;</p>
			<p>&nbsp;</p>
			<p>&nbsp;</p>
		</div>
	</body>
</html>
