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The Effect of Exercise on Plasma Leptin Concentrations in Horses
Journal of Equine Veterinary Science 47 (2016) 36–41
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Review Article
The Effect of Exercise on Plasma Leptin Concentrations in Horses Witold Ke˛ dzierski* Department of Animal Biochemistry and Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Lublin, Poland
a r t i c l e i n f o
a b s t r a c t
Article history: Received 4 July 2016 Received in revised form 4 August 2016 Accepted 4 August 2016 Available online 12 August 2016
Leptin is an adipokine released by adipose tissue. It regulates food intake, energy expenditure, breeding efficiency and the mood of horses. Exercise can influence leptin secretion via changes in the endocrine profile and energy balance. Several studies which describe exercise induced changes in plasma leptin concentrations in horses gave contradictory results. This paper presents a detailed analysis of the effect of exercise and training on plasma leptin concentrations in horses that underwent various types of physical effort. The effect of exercise depends on its intensity and duration as well as on the horse’s sex and performance. Relatively intensive exercise lasting at least 45 minutes increases plasma leptin concentrations in young or irregularly trained horses but not in well trained, performing horses. In well trained horses, plasma leptin concentration does not change during a year, regardless of type of daily exercise. Training decreases the level of this adipokine in young, intensively trained horses and/or neutralizes a tendency for the circulating leptin level to increase in adult horses during a pasture season. Therefore, the level of this adipokine should be monitored, especially in young and intensively trained race horses. Ó 2016 Elsevier Inc. All rights reserved.
Keywords: Exercise Horses Leptin Training
1. Introduction In horses, as in other mammals, leptin is an adipose tissue-derived protein, classified as adipokine. The blood plasma leptin concentration reflects the body fat stores [1,2]. The concentration of this adipokine in plasma was higher in horses with a higher body condition score (BCS) than in slim, fit horses [3–5]. The circulating leptin level informs the central nervous system about the energy status of the organism and regulates appetite and energy processes (Fig. 1). Specifically, leptin inhibits appetite and food intake, and enhances the energy expenditure by increasing both the lipolysis rate in adipocytes and fatty acids oxidation in the liver [6] (Table 1). Even though the body fat mass does not change, some fluctuations in plasma leptin * Corresponding author at: Witold Ke˛ dzierski, Department of Animal Biochemistry and Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka 12, Lublin 20-033, Poland. E-mail address: [email protected]. 0737-0806/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jevs.2016.08.003
concentrations occurred simply in response to short-time changes in the energy balance [7]. Thus, a decrease in the leptin level induced by feed restriction increased hunger and food intake. Moreover, a low plasma leptin concentration was associated with behavioural and metabolic disorders in horses, such as crib-biting and mortality of new born foals [8,9]. On the other hand, an elevated level of this adipokine was found in horses suffering from insulin resistance [10–12]. Leptin is also involved in the regulation of reproductive processes in mares. Lowering BCS and plasma leptin concentrations via nutrient restriction resulted in a decrease in the number of ovarian follicles and profound seasonal anovulatory period in mares [1]. An increase in body weight and/or the plasma leptin concentration increased the estradiol level [13] and induced ovarian activity [14,15]. Namely, leptin regulates reproductive function mainly by an action mediated by neuropeptide Y (NPY). Generally, NPY inhibits gonadotropin hormone (GnRH) secretion from hypothalamus. Leptin supresses NPY release, which action increases GnRH
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Fig. 1. Regulation of leptin synthesis and action of leptin on the brain and peripheral tissues.
release and FSH and LH release from hypophysis (Fig. 1). Thus, the influence of leptin on the horse’s organism has multidirectional character. Changes in plasma leptin concentration in horses can influence their mood, food intake, energy balance and breeding efficiency. Horses are domestic animals generally used for different kinds of work, such as classic horsemanship, races, endurance rides, work in harness and many others. However, only few studies have been focused on the influence of physical exercise on leptin release (Table 2). Due to the importance of biochemistry of physical exercise on horses themselves as well as on economic use of these animals this paper aims at the review and analysis of available knowledge related to the effect of exercise and training on plasma leptin concentrations in working horses.
Table 1 Metabolic effects of changes in leptin level. Metabolic Effects
Decrease in Leptin Level
Increase in Leptin Level
Appetite and food intake Energy expenditure Lipolysis rate Fatty acids oxidation Glucose utilization Ovarian activity Mood
[ Y Y Y Y Y Y
Y [ [ [ [ [ [
2. Hormonal Regulation of Leptin Synthesis and Release Body fat mass is not the only factor which influences plasma leptin concentration. Daily fluctuations in energy status involved transient changes in circulating leptin levels, while body weight and body fat mass remained unchanged [7]. Plasma leptin concentrations decreased in response to feed deprivation, and increased following a meal [7,31,32]. This means that leptin concentrations in circulating blood are not only a simply function of body fat mass. Leptin release by adipose tissue responds to changes in body energy balance because it is controlled by hormones, which regulate energy metabolism: corticosteroids, insulin and catecholamines [33]. Corticosteroids and insulin stimulate leptin synthesis and release, whereas adrenaline plays an opposite role. However, the in vitro studies found only a small stimulatory effect of insulin on leptin release from adipocytes in comparison to the marked increase in leptin synthesis and release due to corticosteroids [34]. In in vivo studies, the infusion of dexamethasone (a synthetic corticosteroid similar to natural cortisol) in therapeutic doses always induced an increase in the plasma leptin concentration in horses [18,35–37]. A rise in cortisol secretion after endotoxin treatment or feed intake also resulted in increased leptin secretion [38,39]. Moreover, feed restriction decreased cortisol as well as leptin levels in horses [40].
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W. Ke˛ dzierski / Journal of Equine Veterinary Science 47 (2016) 36–41
Table 2 Effects of exercise and training on plasma leptin concentration in horses. Changes in Plasma Leptin Concentration Single bout of exercise Leptin Y 24 hours after the exercise [16] Leptin Y immediately after the exercise [17] No effect [18–21] No effect [21] Leptin [ immediately after the exercise [22,23] Leptin [ immediately after the exercise [20] Training or pasturing Leptin [ [24–26] No effect [27,28] Leptin Y [22,28–30]
Exercise induces an increase in cortisol and catecholamines secretion, and a decrease in the insulin level. The ratio of changes in the levels of hormones regulating energy metabolism depends on the relative intensity and duration of the performed exercise [16,41]. Thus, the final effect of exercise on the plasma leptin concentration depends on the type of certain exercise. 3. The Influence of a Single Bout of Exercise Studies which describe exercise induced changes in plasma leptin concentrations have shown contradictory results. In regularly trained Standardbred mares, a decrease in the circulating leptin concentration was only noted 24 hours after short-time, intensive exercise [16]. A transient decrease in the plasma leptin concentration was also noted in Thoroughbred race horses immediately after the end of gallop [17]. Some other studies reported that exercise had no effect on plasma leptin concentrations (for example: [18–20,42]). A detailed study of these manuscripts indicated that the studied horses varied in age and performed different kinds of exercise. Namely, Cartmill et al. [18] and Piccione et al. [19] did not find any influence of exercise on plasma leptin levels. In fact, the horses used in these studies were adults, about ten year old, and the exercise they performed was not very intensive and included 5 minutes lunging [18] or 17 minutes of walk, trot, gallop and jumping trial [19]. Similarly, no leptin response to the training session was noted in well trained, adult jumping and dressage horses, as well as in young Thoroughbred race horses [20]. The effect of more intensive and exhaustive ska [21]. exercise was studied by Ke˛ dzierski and Cywin These researchers examined young and adult Purebred Arabian horses during race training sessions, and endurance competitions, respectively. They also found that both short-term high-intensity exercise and endurance effort did not influence circulating leptin levels. On the other hand, Ke˛ dzierski and Kapica [22] and Gordon et al. [23] have described a significant increase in the level of this adipokine just after Standardbred horses had been exercised. In these studies, young, two to three year old horses, trained for trotting races were included. Their training session consisted of a 45 minute trot with a mean speed achieving value 6.2 m/second [22]. Long-lasting (2.5 hours), middle-intensive exercise in harness also involved an
Horses and Type of Exercise or Training Adult Standardbred, short-term exercise Young Thoroughbred, short-term exercise Young and adult horses of different breeds, short-term exercise Adult Purebred Arabian horses, endurance Young Standardbred, 45 minutes of exercise Adult, irregularly trained horses Untrained, pastured equids Sport horses, daily exercise not very intensive Young and adult horses, intensive training
increase in plasma leptin concentrations in adult draft horses used on an agritourism farm [20]. To sum up this paragraph, an increase in the plasma leptin concentration took place only in young or irregularly trained horses when the exercise was relatively intensive and lasted at least 45 minutes. In well trained, adult horses, even long-lasting, intensive exercise did not cause any fluctuations in circulating leptin concentration, even though the cortisol release was elevated. Thus, the factors influencing the plasma leptin concentration in exercised horses are the duration of exercise, and the horse’s performance. Only the long-lasting exercise leads to the increase in leptin release in young or irregularly trained horses. Probably, the exercise-induced increase in circulating cortisol is the factor which resulted in leptin release from adipocytes in these horses. A short-lasting, intensive exercise causes rather in catecholamines secretion, which inhibits leptin synthesis. 4. Influence of Training The term “training” means developing the physical fitness of horses as a long lasting process by using a training-program which includes gradually increasing the work-load. In Europe, most athletic and race horses are intensively trained from spring to autumn, and rest during the winter. Standardbred trotters, however, are regularly trained and used in races throughout the whole year. In untrained, pastured mares and female donkeys, a tendency for increased plasma leptin concentrations was observed from spring to summer, while a decrease was noted in winter [24–26]. These fluctuations in circulating leptin corresponded positively with the photoperiod and pasture quality [25,26]. It should be noted that, generally, professionally trained horses have no access to pasture and spend most of their time in stables. In trained horses, regularly performed exercise influences the energy status, endocrine profile and horse fitness, which are the factors regulating leptin synthesis and release. Nevertheless, Carter et al. [27] did not observe any effect of moderate exercise training on plasma leptin concentrations in overweight, insulin resistant horses. Also in horses used in classical equestrian sports, plasma leptin concentrations were stable from spring to autumn [28]. The horses studied by Carter et al. [27] and Ke˛ dzierski [28] were adult, and their daily exercise was not very intensive. For one hour a day they walked,
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trotted and cantered or they were involved in showjumping training for low class events. Ke˛ dzierski and Kapica [22] reported that plasma leptin concentrations in young Standardbred horses tended to decrease when observed from winter to summer. A similar effect was described in trained Iberian show horses [29], and in unfit, adult Standardbred horses trained from June to October [30]. These observations suggest that training influences the plasma leptin level in athletic horses, in comparison to untrained, pastured equids. This was confirmed by Ke˛ dzierski [28], which found that plasma leptin concentrations decreased about 10-fold in three-year old Purebred Arabian horses during their first season of training, without any significant changes in their plasma cortisol concentrations and BCS. The results of some studies suggest that, in mammals, tissue sensitivity to cortisol decreases with age and with time spent training via downregulation of glucocorticoid receptor synthesis [43–46]. The downregulation of this receptor synthesis is the tissue response to long-lasting exposure to cortisol elevation induced by training. Thus, training can lead to the decrease in the number of glucocorticoid receptors in cells, including adipocytes, and therefore, cortisol-induced leptin release decreases together with time utilized for training. As a result, intensive training decreases plasma leptin concentrations in naïve horses and/or stabilizes the value of this parameter in horses being trained longer than one year [28]. 5. Effect of a Horse’s Sex In equestrian sports and races, stallions, mares and geldings can compete together, regardless of sex. However, sex steroid hormones influenced leptin release as well as lipid metabolism. In humans, testosterone inhibits leptin secretion and estradiol stimulates the release of leptin independently of body fat mass [47,48]. Moreover, exercise led to increased testosterone levels in stallions, whereas it decreased the plasma estradiol concentrations in mares [49,50]. Thus, it can be expected that exercise can influence the leptin secretion via variations in testosterone and estradiol levels. Generally, adult mares have higher resting plasma leptin concentrations than stallions because of their higher body fat mass or BCS [35]. Experimental injection of dexamethasone increased plasma leptin concentrations in mares and geldings [18], as well as in stallions [37]. A comparative study of the response of stallions and mares to dexamethasone injections showed that the leptin response was higher in mares than in stallions even though their resting values of leptin, BCS or age did not differ [35]. Nevertheless, mares which were treated with testosterone for 10 days, in doses which produced plasma testosterone concentrations similar to those found in reproductive stallions, did not have altered leptin concentrations [35]. In young, fit Standardbred trotters, the plasma leptin concentrations increased in response to training sessions to a greater extent in fillies than in colts [22]. Moreover, the plasma leptin concentration was higher in mares than in geldings, while the values found in stallions were on an intermediate level [50]. The authors concluded that
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castration of stallions caused a decrease in leptin secretion and led to a less effective use of fatty acids as a source of energy produced during exercise. On the other hand, it is known that the effectiveness of fatty acids utilization increases during the time spent training due an increase in the activity of enzymes which are involved in fatty acids oxidation. 6. Potential Importance of Leptin Fluctuations for the Equine Health Leptin receptors were found in most of tissues, which is evidence of the multiplicity of leptin functions. This adipokine influences not only food intake and energy expenditure but also stimulates growth hormone secretion and the development of the brain [51]. There is evidence that in mammals, plasma leptin concentrations correlated positively with the mood and/or with the frame of mind of the studied individuals [9,52–54]. The results of these studies suggest that decreased leptin level can have a negative effect on the mood. On the other hand, low plasma leptin concentrations in laboratory animals and humans are related to low levels of reactive oxygen species, and vice versa, elevated leptin levels are accompanied by oxidative stress [55–57]. Also in horses, high plasma leptin concentrations were found in horses which had a reduced capacity to modulate oxidative stress [12]. However, other in vitro studies found that leptin increases the antioxidant capacity of cells [58,59]. The influence of leptin on the oxidative status was finally explained by Bilbao et al. [60]. These authors discovered that at low concentrations, leptin plays a protective role against oxidative stress, whereas at elevated levels, this adipokine is involved in cell death. Also SamuelMendelsohn et al. [61] showed that leptin induces apoptosis in some cancer cell lines. Generally, the issue of cancer and leptin crosstalk is noteworthy but is far beyond the aim of this review. There is much evidence that in laboratory animals and humans, leptin is involved in cancer development [62–66]. From this point of view, high levels of leptin can adversely affect a mammal’s health. Therefore, training can be beneficial for the health because it decreases plasma leptin concentration. 7. Summary Relatively intensive exercise lasting at least 45 minutes increases plasma leptin concentrations in young horses, and in adult but irregularly trained horses. In adult and well trained horses, the exercise performed does not influence the level of this adipokine. Training could significantly decrease plasma leptin concentrations in naïve horses. It is known that leptin regulates appetite, some aspects of health, and the mood of an animal. Therefore, the level of this adipokine should be monitored, especially in young and intensively trained race horses. References [1] Gentry LR, Thompson Jr DL, Gentry Jr GT, Davis KA, Godke RA, Cartmill JA. The relationship between body condition, leptin, and
40
[2]
[3]
[4]
[5]
[6] [7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
W. Ke˛ dzierski / Journal of Equine Veterinary Science 47 (2016) 36–41 reproductive and hormonal characteristics of mares during the seasonal anovulatory period. J Anim Sci 2002;80:2695–703. Kearns CF, McKeever KH, Roegner V, Brady SM, Malinowski K. Adiponectin and leptin are related to fat mass in horses. Vet J 2006; 172:460–5. Buff PR, Dodds AC, Morrison CD, Whitley NC, McFadin EL, Daniel JA, Djiane J, Keisler DH. Leptin in horses: tissue localization and relationship between peripheral concentrations of leptin and body condition. J Anim Sci 2002;80:2942–8. Gordon ME, McKeever KH, Betros CL, Manso-Filho HC. Plasma leptin, ghrelin and adiponectin concentrations in young fit racehorses versus mature unfit Standardbreds. Vet J 2007;173:91–100. Suagee JK, Corl BA, Crisman MV, Pleasant RS, Thatcher CD, Geor RJ. Relationship between body condition score and plasma inflammatory cytokines, insulin, and lipids in a mixed population of lightbreed horses. J Vet Intern Med 2013;27:157–63. Ramsay TG. Porcine leptin alters insulin inhibition of lipolysis in porcine adipocytes in vitro. J Anim Sci 2001;79:653–765. Van Weyenberg S, Hesta M, Buyse J, Papadopoulos GA, Janssens GPJ. Short-term effects of energy changes on plasma leptin concentrations and glucose tolerance in healthy ponies. Vet J 2008;178: 233–7. Barsnick RJ, Hurcombe SD, Smith PA, Slovis NM, Sprayberry KA, Saville WJ, Toribio RE. Insulin, glucagon, and leptin in critically ill foals. J Vet Intern Med 2011;25:123–31. Hemmann KE, Koho NM, Vainio OM, Raekallio MR. Effects of feed on plasma leptin and ghrelin concentrations in crib-biting horses. Vet J 2013;198:122–6. Frank N, Elliott SB, Brandt LE, Keisler DH. Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese horses with insulin resistance. J Am Vet Med Assoc 2006;228: 1383–90. Carter RA, McCutcheon LJ, George LA, Smith TL, Frank N, Geor RJ. Effects of diet-induced weight gain on insulin sensitivity and plasma hormone and lipid concentrations in horses. Am J Vet Res 2009;70: 1250–8. Pleasant RS, Suagee JK, Thatcher CD, Elvinger F, Geor RJ. Adiposity, plasma insulin, leptin, lipids, and oxidative stress in mature light breed horses. J Vet Intern Med 2013;27:576–82. El-Maaty AM, Gabr FI. Relation between leptin and estradiol levels in Egyptian lactating Arab mares during foaling heat. Anim Reprod Sci 2010;117:95–8. Ferreira-Dias G, Claudino F, Carvalho H, Agrícola R, AlpoimMoreira J, Robalo Silva J. Seasonal reproduction in the mare: possible role of plasma leptin, body weight and immune status. Domest Anim Endocrinol 2005;29:203–13. Vizuete G, Diez E, Galisteo J, Agüera E, Aguilera-Tejero E, PerezMarín CC. Comparison of different treatments for oestrous induction in seasonally anovulatory mares. Reprod Domest Anim 2013;48: 463–9. Gordon ME, McKeever KH, Betros CL, Manso-Filho HC. Exerciseinduced alterations in plasma concentrations of ghrelin, adiponectin, leptin, glucose, insulin, and cortisol in horses. Vet J 2007; 173:532–40. Ke˛ dzierski W. Effect of exercise on plasma leptin level in sport and race horses. Xiv Congress of Polish Society of Veterinary Sciences, Conference materials, Copyright by Uniwersytet Przyrodniczy we Wrocławiu. Wrocław 2012;2012:140. Cartmill JA, Thompson Jr DL, Storer WA, Gentry LR, Huff NK. Endocrine responses in mares and geldings with high body condition scores grouped by high vs. low resting leptin concentrations. J Anim Sci 2003;81:2311–21. Piccione G, Grasso F, Costa A, Fazio F, Caola G. Influence of shortterm exercise on serum leptin concentration in the horse. Vet Arh 2005;75:15–22. Ke˛ dzierski W. Changes in plasma leptin concentration during different types of exercise performed by horses. Animal 2014;8: 1456–61. ska A. The effect of different physical exercise Ke˛ dzierski W, Cywin on plasma leptin, cortisol, and some energetic parameters concentrations in Purebred Arabian horses. J Equine Vet Sci 2014;34: 1059–63. Ke˛ dzierski W, Kapica M. Plasma concentration of leptin and ghrelin in Standardbred foals as related to the age, sex, exercise and training. Animal 2008;2:582–7. Gordon ME, McKeever KH, Bokman S, Betros CL, Manso-Filho HC, Liburt N, Streltsova J. Interval exercise alters feed intake as well as leptin and ghrelin concentrations in Standardbred mares. Equine Vet J Suppl 2006;36:596–605.
[24] Cebulj-Kadunc N, Cestnik V. The influence of season and age on circulating melatonin and leptin concentrations in Lipizzan fillies. Acta Vet (Beogr) 2008;58:25–31. [25] Cebulj-Kadunc N, Kosec M, Cestnik V. Serum leptin concentrations in Lipizzan fillies. Reprod Domest Anim 2009;44:1–5. [26] Cebulj-Kadunc N, Skibin A, Kosec M. Long-term leptin fluctuations in female donkeys. Equine Vet J 2015;47:731–5. [27] Carter RA, McCutcheon LJ, Valle E, Meilahn EN, Geor RJ. Effects of exercise training on adiposity, insulin sensitivity, and plasma hormone and lipid concentrations in overweight or obese, insulinresistant horses. Am J Vet Res 2010;71:314–21. [28] Ke˛ dzierski W. Leptin fluctuations in trained horses, during a work season. J Equine Vet Sci 2016;43:12–7. [29] Amato C, Martin L, Dumon H, Jaillardon L, Nguyen P, Siliart B. Variations in plasma leptin in show horses during a work season. J Anim Physiol Anim Nutr (Berl) 2012;96:850–9. [30] Aulisio JL, Liburt NR, Malinowski K, McKeever KH. Training-induced alternations in rump fat thickness and plasma leptin concentration in young mature and old Standardbred mares. Comp Exerc Physiol 2011;7:127–32. [31] Buff PR, Morrison CD, Ganjam VK, Keisler DH. Effects of short-term feed deprivation and melatonin implants on circadian patterns of leptin in the horse. J Anim Sci 2005;83:1023–32. [32] Gastal MO, Gastal EL, Beg MA, Ginther OJ. Short-term feed restriction decreases the systemic and intrafollicular concentrations of leptin and increases the vascularity of the preovulatory follicle in mares. Theriogenology 2010;73:1202–9. [33] Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 2004;50:1511–25. [34] Fain JN, Bahnouth SW. Regulation of leptin release by mammalian adipose tissue. Biochem Biophys Res Commun 2000;274:571–5. [35] Cartmill JA, Thompson Jr DL, Del Vecchio RP, Storer WA, Crowley JC. Leptin secretion in horses: effects of dexamethasone, gender, and testosterone. Domest Anim Endocrinol 2006;31:197–210. [36] Cartmill JA, Thompson Jr DL, Gentry LR, Pruett HE, Johnson CA. Effects of dexamethasone, glucose infusion, adrenocorticotropin, and propylthiouracil on plasma leptin concentrations in horses. Domest Anim Endocrinol 2003;24:1–14. [37] Cartmill JA, Thompson Jr DL, Storer WA, Crowley JC, Huff NK, Waller CA. Effect of dexamethasone, feeding time, and insulin infusion on leptin concentrations in stallions. J Anim Sci 2005;83: 1875–81. [38] Huff NK, Thompson Jr DL, Mitcham PB, Storer WA. Hyperleptinemia in horses: responses to administration of a small dose of lipopolysaccharide endotoxin in mares and geldings. J Anim Sci 2010;88: 926–36. [39] Van Weyenberg S, Buyse J, Kalmar ID, Swennen Q, Janssens GPJ. Voluntary feed intake and leptin sensitivity in ad libitum fed obese ponies following a period of restricted feeding: a pilot study. J Anim Physiol Anim Nutr 2013;97:624–31. [40] Glunk EC, Hathaway MR, Grev AM, Lamprecht ED, Mather MC, Martinson KL. The effect of a limit-fed diet and slow-feed hay nets on morphometric measurements and postprandial metabolite and hormone patterns in adult horses. J Anim Sci 2015;93:4144–52. [41] Desmecht D, Linden A, Amory H, Art T, Lekeux P. Relationship of plasma lactate production to cortisol release following completion of different types of sporting events in horses. Vet Res Commun 1996;20:371–9. [42] Piccione G, Bertolucci C, Foa A, Caola G. Influence of fasting and exercise on the daily rhytm of serum leptin in the horse. Chronobiol Int 2004;21:405–17. [43] Campbell JE, Fediuc S, Hawke TJ, Riddell MC. Endurance exercise training increases adipose tissue glucocorticoid exposure: adaptations that facilitate lipolysis. Metabolism 2009;58:651–60. [44] Bonifazi M, Mencarelli M, Fedele V, Ceccarelli I, Pecorelli A, Grasso G, Aloisi AM, Muscettola M. Glucocorticoid receptor mRNA expression in peripheral blood mononuclear cells in high trained compared to low trained athletes and untrained subjects. J Endocrinol Invest 2009;32:816–20. [45] Fragala MS, Kraemer WJ, Mastro AM, Denegar CR, Volek JS, Kupchak BR, Häkkinen K, Anderson JM, Maresh CM. Glucocorticoid receptor expression on human B cells in response to acute heavy resistance exercise. Neuroimmunomodulation 2011;18: 156–64. [46] Boscaro M, Paoletta A, Scarpa E, Barzon L, Fusaro P, Falla F, Sonino N. Age-related changes in glucocorticoid fast feedback inhibition of adrenocorticotropin in man. J Clin Endocrinol Metab 1998;83: 1380–3.
W. Ke˛ dzierski / Journal of Equine Veterinary Science 47 (2016) 36–41 [47] Büchter D, Behre HM, Kliesch S, Chirazi A, Nieschlag E, Assmann G, von Eckardstein A. Effects of testosterone suppression in young men by the gonadotropin releasing hormone antagonist cetrorelix on plasma lipids, lipolytic enzymes, lipid transfer proteins, insulin, and leptin. Exp Clin Endocrinol Diabetes 1999;107:522–9. [48] Puder JJ, Monaco SE, Sen Gupta S, Wang J, Ferin M, Warren MP. Estrogen and exercise may be related to body fat distribution and leptin in young women. Fertil Steril 2006;86:694–9. [49] Janett F, Burkhardt C, Burger D, Imboden I, Hässig M, Thun R. Influence of repeated treadmill exercise on quality and freezability of stallion semen. Theriogenology 2006;65:1737–49. [50] Ke˛ dzierski W, Kowalik S. Leptin and ghrelin and the indices of lipid metabolism as related to sex steroid hormones in trotters. J Equine Vet Sci 2009;29:17–23. [51] Mácajová M, Lamosová D, Zeman M. Role of leptin in farm animals: a review. J Vet Med a Physiol Pathol Clin Med 2004;51:157–66. [52] Skalkidou A, Sylvén SM, Papadopoulos FC, Olovsson M, Larsson A, Sundström-Poromaa I. Risk of postpartum depression in association with serum leptin and interleukin-6 levels at delivery: a nested case-control study within the UPPSAT cohort. Psychoneuroendocrinology 2009;34:1329–37. [53] Kalbe C, Puppe B. Long-term cognitive enrichment affects opioid receptor expression in the amygdala of domestic pigs. Genes Brain Behav 2010;9:75–83. [54] Wickham SL, Collins T, Barnes AL, Miller DW, Beatty DT, Stockman CA, Blache D, Wemelsfelder F, Fleming PA. Validating the use of qualitative behavioral assessment as a measure of the welfare of sheep during transport. J Appl Anim Welf Sci 2015;18: 169–86. [55] Kulu S, Canpolat S, Aydin M, Yasar A, Tuzcu M, Baydas G. Exogenous leptin increases lipid peroxidation in the mouse brain. Tohoku J Exp Med 2005;206:233–6. [56] Horoz M, Aslan M, Koylu AO, Bolukbas C, Bolukbas FF, Selek S, Erel O. The relationship between leptin level and oxidative status parameters in hemodialysis patients. Artif Organs 2009;33:81–5. [57] Habib SA, Saad EA, Elsharkawy AA, Attia ZR. Pro-inflamatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with
[58]
[59]
[60]
[61]
[62]
[63]
[64]
[65]
[66]
41
obesity in Egyptian non-diabetic obese children and adolescents. Adv Med Sci 2015;60:179–85. Zwirska-Korczala K, Adamczyk-Sowa M, Sowa P, Pilc K, Suchanek R, Pierzchala K, Namyslowski G, Misiolek M, Sodowski K, Kato I, Kuwahara A, Zabielski R. Role of leptin, ghrelin, angiotensyn II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism. J Physiol Pharmacol 2007;58(Suppl 1):53–64. Bułdak RJ, Pilc-Gumuła K, Bułdak Ł, Witkowska D, Kukla M, Polaniak R, Zwirska-Korczala K. Effects of ghrelin, leptin and melatonin on the levels of reactive oxygen species, antioxidant enzyme activity and viability of the HCT 116 human colorectal carcinoma cell line. Mol Med Rep 2015;12:2275–82. Bilbao MG, Di Yorio MP, Galarza RA, Varone CL, Faletti AG. Regulation of the ovarian oxidative status by leptin during the ovulatory process in rats. Reproduction 2015;149:357–66. Samuel-Mendelsohn S, Inbar M, Weiss-Messer E, Niv-Spector L, Gertel A, Barkey RJ. Leptin signaling and apoptotic effects in human prostate cancer cell lines. Prostate 2011;71:929–45. Dogan S, Hu X, Zhang Y, Maihle NJ, Grande JP, Clearly MP. Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-alpha mice. Breast Cancer Res 2007;9:R91. Ray A, Nkhata KJ, Cleary MP. Effects of leptin on human breast cancer cell lines in relationship to estrogen receptor and HER2 status. Int J Oncol 2007;30:1499–509. Fiorio E, Mercanti A, Terrasi M, Micciolo R, Remo A, Auriemma A, Molino A, Parolin V, Di Stefano B, Bonetti F, Giordano A, Cetto GL, Surmacz E. Leptin/HER2 crosstalk in brest cancer: in vitro study and preliminary in vivo analysis. BMC Cancer 2008;8:305. Karaduman M, Bilici A, Ozet A, Sengul A, Musabak U, Alomeroglu M. Tissue leptin levels in patients with breast cancer. J BUON 2010;15: 369–72. Karim S, Merdar A, Achulten HJ, Jayapal M, Dallol A, Buhmeida A, Al-Thubaity F, Mirza Z, Gari MA, Chaudhary AG, Abuzenadah AM, Al-Qahtani MH. Low expression of leptin and its association with breast cancer: a transcriptomic study. Oncol Rep 2016;36:43–8.
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Journal of Equine Veterinary Science journal homepage: www.j-evs.com
Review Article
The Effect of Exercise on Plasma Leptin Concentrations in Horses Witold Ke˛ dzierski* Department of Animal Biochemistry and Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Lublin, Poland
a r t i c l e i n f o
a b s t r a c t
Article history: Received 4 July 2016 Received in revised form 4 August 2016 Accepted 4 August 2016 Available online 12 August 2016
Leptin is an adipokine released by adipose tissue. It regulates food intake, energy expenditure, breeding efficiency and the mood of horses. Exercise can influence leptin secretion via changes in the endocrine profile and energy balance. Several studies which describe exercise induced changes in plasma leptin concentrations in horses gave contradictory results. This paper presents a detailed analysis of the effect of exercise and training on plasma leptin concentrations in horses that underwent various types of physical effort. The effect of exercise depends on its intensity and duration as well as on the horse’s sex and performance. Relatively intensive exercise lasting at least 45 minutes increases plasma leptin concentrations in young or irregularly trained horses but not in well trained, performing horses. In well trained horses, plasma leptin concentration does not change during a year, regardless of type of daily exercise. Training decreases the level of this adipokine in young, intensively trained horses and/or neutralizes a tendency for the circulating leptin level to increase in adult horses during a pasture season. Therefore, the level of this adipokine should be monitored, especially in young and intensively trained race horses. Ó 2016 Elsevier Inc. All rights reserved.
Keywords: Exercise Horses Leptin Training
1. Introduction In horses, as in other mammals, leptin is an adipose tissue-derived protein, classified as adipokine. The blood plasma leptin concentration reflects the body fat stores [1,2]. The concentration of this adipokine in plasma was higher in horses with a higher body condition score (BCS) than in slim, fit horses [3–5]. The circulating leptin level informs the central nervous system about the energy status of the organism and regulates appetite and energy processes (Fig. 1). Specifically, leptin inhibits appetite and food intake, and enhances the energy expenditure by increasing both the lipolysis rate in adipocytes and fatty acids oxidation in the liver [6] (Table 1). Even though the body fat mass does not change, some fluctuations in plasma leptin * Corresponding author at: Witold Ke˛ dzierski, Department of Animal Biochemistry and Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka 12, Lublin 20-033, Poland. E-mail address: [email protected]. 0737-0806/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jevs.2016.08.003
concentrations occurred simply in response to short-time changes in the energy balance [7]. Thus, a decrease in the leptin level induced by feed restriction increased hunger and food intake. Moreover, a low plasma leptin concentration was associated with behavioural and metabolic disorders in horses, such as crib-biting and mortality of new born foals [8,9]. On the other hand, an elevated level of this adipokine was found in horses suffering from insulin resistance [10–12]. Leptin is also involved in the regulation of reproductive processes in mares. Lowering BCS and plasma leptin concentrations via nutrient restriction resulted in a decrease in the number of ovarian follicles and profound seasonal anovulatory period in mares [1]. An increase in body weight and/or the plasma leptin concentration increased the estradiol level [13] and induced ovarian activity [14,15]. Namely, leptin regulates reproductive function mainly by an action mediated by neuropeptide Y (NPY). Generally, NPY inhibits gonadotropin hormone (GnRH) secretion from hypothalamus. Leptin supresses NPY release, which action increases GnRH
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Fig. 1. Regulation of leptin synthesis and action of leptin on the brain and peripheral tissues.
release and FSH and LH release from hypophysis (Fig. 1). Thus, the influence of leptin on the horse’s organism has multidirectional character. Changes in plasma leptin concentration in horses can influence their mood, food intake, energy balance and breeding efficiency. Horses are domestic animals generally used for different kinds of work, such as classic horsemanship, races, endurance rides, work in harness and many others. However, only few studies have been focused on the influence of physical exercise on leptin release (Table 2). Due to the importance of biochemistry of physical exercise on horses themselves as well as on economic use of these animals this paper aims at the review and analysis of available knowledge related to the effect of exercise and training on plasma leptin concentrations in working horses.
Table 1 Metabolic effects of changes in leptin level. Metabolic Effects
Decrease in Leptin Level
Increase in Leptin Level
Appetite and food intake Energy expenditure Lipolysis rate Fatty acids oxidation Glucose utilization Ovarian activity Mood
[ Y Y Y Y Y Y
Y [ [ [ [ [ [
2. Hormonal Regulation of Leptin Synthesis and Release Body fat mass is not the only factor which influences plasma leptin concentration. Daily fluctuations in energy status involved transient changes in circulating leptin levels, while body weight and body fat mass remained unchanged [7]. Plasma leptin concentrations decreased in response to feed deprivation, and increased following a meal [7,31,32]. This means that leptin concentrations in circulating blood are not only a simply function of body fat mass. Leptin release by adipose tissue responds to changes in body energy balance because it is controlled by hormones, which regulate energy metabolism: corticosteroids, insulin and catecholamines [33]. Corticosteroids and insulin stimulate leptin synthesis and release, whereas adrenaline plays an opposite role. However, the in vitro studies found only a small stimulatory effect of insulin on leptin release from adipocytes in comparison to the marked increase in leptin synthesis and release due to corticosteroids [34]. In in vivo studies, the infusion of dexamethasone (a synthetic corticosteroid similar to natural cortisol) in therapeutic doses always induced an increase in the plasma leptin concentration in horses [18,35–37]. A rise in cortisol secretion after endotoxin treatment or feed intake also resulted in increased leptin secretion [38,39]. Moreover, feed restriction decreased cortisol as well as leptin levels in horses [40].
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W. Ke˛ dzierski / Journal of Equine Veterinary Science 47 (2016) 36–41
Table 2 Effects of exercise and training on plasma leptin concentration in horses. Changes in Plasma Leptin Concentration Single bout of exercise Leptin Y 24 hours after the exercise [16] Leptin Y immediately after the exercise [17] No effect [18–21] No effect [21] Leptin [ immediately after the exercise [22,23] Leptin [ immediately after the exercise [20] Training or pasturing Leptin [ [24–26] No effect [27,28] Leptin Y [22,28–30]
Exercise induces an increase in cortisol and catecholamines secretion, and a decrease in the insulin level. The ratio of changes in the levels of hormones regulating energy metabolism depends on the relative intensity and duration of the performed exercise [16,41]. Thus, the final effect of exercise on the plasma leptin concentration depends on the type of certain exercise. 3. The Influence of a Single Bout of Exercise Studies which describe exercise induced changes in plasma leptin concentrations have shown contradictory results. In regularly trained Standardbred mares, a decrease in the circulating leptin concentration was only noted 24 hours after short-time, intensive exercise [16]. A transient decrease in the plasma leptin concentration was also noted in Thoroughbred race horses immediately after the end of gallop [17]. Some other studies reported that exercise had no effect on plasma leptin concentrations (for example: [18–20,42]). A detailed study of these manuscripts indicated that the studied horses varied in age and performed different kinds of exercise. Namely, Cartmill et al. [18] and Piccione et al. [19] did not find any influence of exercise on plasma leptin levels. In fact, the horses used in these studies were adults, about ten year old, and the exercise they performed was not very intensive and included 5 minutes lunging [18] or 17 minutes of walk, trot, gallop and jumping trial [19]. Similarly, no leptin response to the training session was noted in well trained, adult jumping and dressage horses, as well as in young Thoroughbred race horses [20]. The effect of more intensive and exhaustive ska [21]. exercise was studied by Ke˛ dzierski and Cywin These researchers examined young and adult Purebred Arabian horses during race training sessions, and endurance competitions, respectively. They also found that both short-term high-intensity exercise and endurance effort did not influence circulating leptin levels. On the other hand, Ke˛ dzierski and Kapica [22] and Gordon et al. [23] have described a significant increase in the level of this adipokine just after Standardbred horses had been exercised. In these studies, young, two to three year old horses, trained for trotting races were included. Their training session consisted of a 45 minute trot with a mean speed achieving value 6.2 m/second [22]. Long-lasting (2.5 hours), middle-intensive exercise in harness also involved an
Horses and Type of Exercise or Training Adult Standardbred, short-term exercise Young Thoroughbred, short-term exercise Young and adult horses of different breeds, short-term exercise Adult Purebred Arabian horses, endurance Young Standardbred, 45 minutes of exercise Adult, irregularly trained horses Untrained, pastured equids Sport horses, daily exercise not very intensive Young and adult horses, intensive training
increase in plasma leptin concentrations in adult draft horses used on an agritourism farm [20]. To sum up this paragraph, an increase in the plasma leptin concentration took place only in young or irregularly trained horses when the exercise was relatively intensive and lasted at least 45 minutes. In well trained, adult horses, even long-lasting, intensive exercise did not cause any fluctuations in circulating leptin concentration, even though the cortisol release was elevated. Thus, the factors influencing the plasma leptin concentration in exercised horses are the duration of exercise, and the horse’s performance. Only the long-lasting exercise leads to the increase in leptin release in young or irregularly trained horses. Probably, the exercise-induced increase in circulating cortisol is the factor which resulted in leptin release from adipocytes in these horses. A short-lasting, intensive exercise causes rather in catecholamines secretion, which inhibits leptin synthesis. 4. Influence of Training The term “training” means developing the physical fitness of horses as a long lasting process by using a training-program which includes gradually increasing the work-load. In Europe, most athletic and race horses are intensively trained from spring to autumn, and rest during the winter. Standardbred trotters, however, are regularly trained and used in races throughout the whole year. In untrained, pastured mares and female donkeys, a tendency for increased plasma leptin concentrations was observed from spring to summer, while a decrease was noted in winter [24–26]. These fluctuations in circulating leptin corresponded positively with the photoperiod and pasture quality [25,26]. It should be noted that, generally, professionally trained horses have no access to pasture and spend most of their time in stables. In trained horses, regularly performed exercise influences the energy status, endocrine profile and horse fitness, which are the factors regulating leptin synthesis and release. Nevertheless, Carter et al. [27] did not observe any effect of moderate exercise training on plasma leptin concentrations in overweight, insulin resistant horses. Also in horses used in classical equestrian sports, plasma leptin concentrations were stable from spring to autumn [28]. The horses studied by Carter et al. [27] and Ke˛ dzierski [28] were adult, and their daily exercise was not very intensive. For one hour a day they walked,
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trotted and cantered or they were involved in showjumping training for low class events. Ke˛ dzierski and Kapica [22] reported that plasma leptin concentrations in young Standardbred horses tended to decrease when observed from winter to summer. A similar effect was described in trained Iberian show horses [29], and in unfit, adult Standardbred horses trained from June to October [30]. These observations suggest that training influences the plasma leptin level in athletic horses, in comparison to untrained, pastured equids. This was confirmed by Ke˛ dzierski [28], which found that plasma leptin concentrations decreased about 10-fold in three-year old Purebred Arabian horses during their first season of training, without any significant changes in their plasma cortisol concentrations and BCS. The results of some studies suggest that, in mammals, tissue sensitivity to cortisol decreases with age and with time spent training via downregulation of glucocorticoid receptor synthesis [43–46]. The downregulation of this receptor synthesis is the tissue response to long-lasting exposure to cortisol elevation induced by training. Thus, training can lead to the decrease in the number of glucocorticoid receptors in cells, including adipocytes, and therefore, cortisol-induced leptin release decreases together with time utilized for training. As a result, intensive training decreases plasma leptin concentrations in naïve horses and/or stabilizes the value of this parameter in horses being trained longer than one year [28]. 5. Effect of a Horse’s Sex In equestrian sports and races, stallions, mares and geldings can compete together, regardless of sex. However, sex steroid hormones influenced leptin release as well as lipid metabolism. In humans, testosterone inhibits leptin secretion and estradiol stimulates the release of leptin independently of body fat mass [47,48]. Moreover, exercise led to increased testosterone levels in stallions, whereas it decreased the plasma estradiol concentrations in mares [49,50]. Thus, it can be expected that exercise can influence the leptin secretion via variations in testosterone and estradiol levels. Generally, adult mares have higher resting plasma leptin concentrations than stallions because of their higher body fat mass or BCS [35]. Experimental injection of dexamethasone increased plasma leptin concentrations in mares and geldings [18], as well as in stallions [37]. A comparative study of the response of stallions and mares to dexamethasone injections showed that the leptin response was higher in mares than in stallions even though their resting values of leptin, BCS or age did not differ [35]. Nevertheless, mares which were treated with testosterone for 10 days, in doses which produced plasma testosterone concentrations similar to those found in reproductive stallions, did not have altered leptin concentrations [35]. In young, fit Standardbred trotters, the plasma leptin concentrations increased in response to training sessions to a greater extent in fillies than in colts [22]. Moreover, the plasma leptin concentration was higher in mares than in geldings, while the values found in stallions were on an intermediate level [50]. The authors concluded that
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castration of stallions caused a decrease in leptin secretion and led to a less effective use of fatty acids as a source of energy produced during exercise. On the other hand, it is known that the effectiveness of fatty acids utilization increases during the time spent training due an increase in the activity of enzymes which are involved in fatty acids oxidation. 6. Potential Importance of Leptin Fluctuations for the Equine Health Leptin receptors were found in most of tissues, which is evidence of the multiplicity of leptin functions. This adipokine influences not only food intake and energy expenditure but also stimulates growth hormone secretion and the development of the brain [51]. There is evidence that in mammals, plasma leptin concentrations correlated positively with the mood and/or with the frame of mind of the studied individuals [9,52–54]. The results of these studies suggest that decreased leptin level can have a negative effect on the mood. On the other hand, low plasma leptin concentrations in laboratory animals and humans are related to low levels of reactive oxygen species, and vice versa, elevated leptin levels are accompanied by oxidative stress [55–57]. Also in horses, high plasma leptin concentrations were found in horses which had a reduced capacity to modulate oxidative stress [12]. However, other in vitro studies found that leptin increases the antioxidant capacity of cells [58,59]. The influence of leptin on the oxidative status was finally explained by Bilbao et al. [60]. These authors discovered that at low concentrations, leptin plays a protective role against oxidative stress, whereas at elevated levels, this adipokine is involved in cell death. Also SamuelMendelsohn et al. [61] showed that leptin induces apoptosis in some cancer cell lines. Generally, the issue of cancer and leptin crosstalk is noteworthy but is far beyond the aim of this review. There is much evidence that in laboratory animals and humans, leptin is involved in cancer development [62–66]. From this point of view, high levels of leptin can adversely affect a mammal’s health. Therefore, training can be beneficial for the health because it decreases plasma leptin concentration. 7. Summary Relatively intensive exercise lasting at least 45 minutes increases plasma leptin concentrations in young horses, and in adult but irregularly trained horses. In adult and well trained horses, the exercise performed does not influence the level of this adipokine. Training could significantly decrease plasma leptin concentrations in naïve horses. It is known that leptin regulates appetite, some aspects of health, and the mood of an animal. Therefore, the level of this adipokine should be monitored, especially in young and intensively trained race horses. References [1] Gentry LR, Thompson Jr DL, Gentry Jr GT, Davis KA, Godke RA, Cartmill JA. The relationship between body condition, leptin, and
40
[2]
[3]
[4]
[5]
[6] [7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
W. Ke˛ dzierski / Journal of Equine Veterinary Science 47 (2016) 36–41 reproductive and hormonal characteristics of mares during the seasonal anovulatory period. J Anim Sci 2002;80:2695–703. Kearns CF, McKeever KH, Roegner V, Brady SM, Malinowski K. Adiponectin and leptin are related to fat mass in horses. Vet J 2006; 172:460–5. Buff PR, Dodds AC, Morrison CD, Whitley NC, McFadin EL, Daniel JA, Djiane J, Keisler DH. Leptin in horses: tissue localization and relationship between peripheral concentrations of leptin and body condition. J Anim Sci 2002;80:2942–8. Gordon ME, McKeever KH, Betros CL, Manso-Filho HC. Plasma leptin, ghrelin and adiponectin concentrations in young fit racehorses versus mature unfit Standardbreds. Vet J 2007;173:91–100. Suagee JK, Corl BA, Crisman MV, Pleasant RS, Thatcher CD, Geor RJ. Relationship between body condition score and plasma inflammatory cytokines, insulin, and lipids in a mixed population of lightbreed horses. J Vet Intern Med 2013;27:157–63. Ramsay TG. Porcine leptin alters insulin inhibition of lipolysis in porcine adipocytes in vitro. J Anim Sci 2001;79:653–765. Van Weyenberg S, Hesta M, Buyse J, Papadopoulos GA, Janssens GPJ. Short-term effects of energy changes on plasma leptin concentrations and glucose tolerance in healthy ponies. Vet J 2008;178: 233–7. Barsnick RJ, Hurcombe SD, Smith PA, Slovis NM, Sprayberry KA, Saville WJ, Toribio RE. Insulin, glucagon, and leptin in critically ill foals. J Vet Intern Med 2011;25:123–31. Hemmann KE, Koho NM, Vainio OM, Raekallio MR. Effects of feed on plasma leptin and ghrelin concentrations in crib-biting horses. Vet J 2013;198:122–6. Frank N, Elliott SB, Brandt LE, Keisler DH. Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese horses with insulin resistance. J Am Vet Med Assoc 2006;228: 1383–90. Carter RA, McCutcheon LJ, George LA, Smith TL, Frank N, Geor RJ. Effects of diet-induced weight gain on insulin sensitivity and plasma hormone and lipid concentrations in horses. Am J Vet Res 2009;70: 1250–8. Pleasant RS, Suagee JK, Thatcher CD, Elvinger F, Geor RJ. Adiposity, plasma insulin, leptin, lipids, and oxidative stress in mature light breed horses. J Vet Intern Med 2013;27:576–82. El-Maaty AM, Gabr FI. Relation between leptin and estradiol levels in Egyptian lactating Arab mares during foaling heat. Anim Reprod Sci 2010;117:95–8. Ferreira-Dias G, Claudino F, Carvalho H, Agrícola R, AlpoimMoreira J, Robalo Silva J. Seasonal reproduction in the mare: possible role of plasma leptin, body weight and immune status. Domest Anim Endocrinol 2005;29:203–13. Vizuete G, Diez E, Galisteo J, Agüera E, Aguilera-Tejero E, PerezMarín CC. Comparison of different treatments for oestrous induction in seasonally anovulatory mares. Reprod Domest Anim 2013;48: 463–9. Gordon ME, McKeever KH, Betros CL, Manso-Filho HC. Exerciseinduced alterations in plasma concentrations of ghrelin, adiponectin, leptin, glucose, insulin, and cortisol in horses. Vet J 2007; 173:532–40. Ke˛ dzierski W. Effect of exercise on plasma leptin level in sport and race horses. Xiv Congress of Polish Society of Veterinary Sciences, Conference materials, Copyright by Uniwersytet Przyrodniczy we Wrocławiu. Wrocław 2012;2012:140. Cartmill JA, Thompson Jr DL, Storer WA, Gentry LR, Huff NK. Endocrine responses in mares and geldings with high body condition scores grouped by high vs. low resting leptin concentrations. J Anim Sci 2003;81:2311–21. Piccione G, Grasso F, Costa A, Fazio F, Caola G. Influence of shortterm exercise on serum leptin concentration in the horse. Vet Arh 2005;75:15–22. Ke˛ dzierski W. Changes in plasma leptin concentration during different types of exercise performed by horses. Animal 2014;8: 1456–61. ska A. The effect of different physical exercise Ke˛ dzierski W, Cywin on plasma leptin, cortisol, and some energetic parameters concentrations in Purebred Arabian horses. J Equine Vet Sci 2014;34: 1059–63. Ke˛ dzierski W, Kapica M. Plasma concentration of leptin and ghrelin in Standardbred foals as related to the age, sex, exercise and training. Animal 2008;2:582–7. Gordon ME, McKeever KH, Bokman S, Betros CL, Manso-Filho HC, Liburt N, Streltsova J. Interval exercise alters feed intake as well as leptin and ghrelin concentrations in Standardbred mares. Equine Vet J Suppl 2006;36:596–605.
[24] Cebulj-Kadunc N, Cestnik V. The influence of season and age on circulating melatonin and leptin concentrations in Lipizzan fillies. Acta Vet (Beogr) 2008;58:25–31. [25] Cebulj-Kadunc N, Kosec M, Cestnik V. Serum leptin concentrations in Lipizzan fillies. Reprod Domest Anim 2009;44:1–5. [26] Cebulj-Kadunc N, Skibin A, Kosec M. Long-term leptin fluctuations in female donkeys. Equine Vet J 2015;47:731–5. [27] Carter RA, McCutcheon LJ, Valle E, Meilahn EN, Geor RJ. Effects of exercise training on adiposity, insulin sensitivity, and plasma hormone and lipid concentrations in overweight or obese, insulinresistant horses. Am J Vet Res 2010;71:314–21. [28] Ke˛ dzierski W. Leptin fluctuations in trained horses, during a work season. J Equine Vet Sci 2016;43:12–7. [29] Amato C, Martin L, Dumon H, Jaillardon L, Nguyen P, Siliart B. Variations in plasma leptin in show horses during a work season. J Anim Physiol Anim Nutr (Berl) 2012;96:850–9. [30] Aulisio JL, Liburt NR, Malinowski K, McKeever KH. Training-induced alternations in rump fat thickness and plasma leptin concentration in young mature and old Standardbred mares. Comp Exerc Physiol 2011;7:127–32. [31] Buff PR, Morrison CD, Ganjam VK, Keisler DH. Effects of short-term feed deprivation and melatonin implants on circadian patterns of leptin in the horse. J Anim Sci 2005;83:1023–32. [32] Gastal MO, Gastal EL, Beg MA, Ginther OJ. Short-term feed restriction decreases the systemic and intrafollicular concentrations of leptin and increases the vascularity of the preovulatory follicle in mares. Theriogenology 2010;73:1202–9. [33] Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 2004;50:1511–25. [34] Fain JN, Bahnouth SW. Regulation of leptin release by mammalian adipose tissue. Biochem Biophys Res Commun 2000;274:571–5. [35] Cartmill JA, Thompson Jr DL, Del Vecchio RP, Storer WA, Crowley JC. Leptin secretion in horses: effects of dexamethasone, gender, and testosterone. Domest Anim Endocrinol 2006;31:197–210. [36] Cartmill JA, Thompson Jr DL, Gentry LR, Pruett HE, Johnson CA. Effects of dexamethasone, glucose infusion, adrenocorticotropin, and propylthiouracil on plasma leptin concentrations in horses. Domest Anim Endocrinol 2003;24:1–14. [37] Cartmill JA, Thompson Jr DL, Storer WA, Crowley JC, Huff NK, Waller CA. Effect of dexamethasone, feeding time, and insulin infusion on leptin concentrations in stallions. J Anim Sci 2005;83: 1875–81. [38] Huff NK, Thompson Jr DL, Mitcham PB, Storer WA. Hyperleptinemia in horses: responses to administration of a small dose of lipopolysaccharide endotoxin in mares and geldings. J Anim Sci 2010;88: 926–36. [39] Van Weyenberg S, Buyse J, Kalmar ID, Swennen Q, Janssens GPJ. Voluntary feed intake and leptin sensitivity in ad libitum fed obese ponies following a period of restricted feeding: a pilot study. J Anim Physiol Anim Nutr 2013;97:624–31. [40] Glunk EC, Hathaway MR, Grev AM, Lamprecht ED, Mather MC, Martinson KL. The effect of a limit-fed diet and slow-feed hay nets on morphometric measurements and postprandial metabolite and hormone patterns in adult horses. J Anim Sci 2015;93:4144–52. [41] Desmecht D, Linden A, Amory H, Art T, Lekeux P. Relationship of plasma lactate production to cortisol release following completion of different types of sporting events in horses. Vet Res Commun 1996;20:371–9. [42] Piccione G, Bertolucci C, Foa A, Caola G. Influence of fasting and exercise on the daily rhytm of serum leptin in the horse. Chronobiol Int 2004;21:405–17. [43] Campbell JE, Fediuc S, Hawke TJ, Riddell MC. Endurance exercise training increases adipose tissue glucocorticoid exposure: adaptations that facilitate lipolysis. Metabolism 2009;58:651–60. [44] Bonifazi M, Mencarelli M, Fedele V, Ceccarelli I, Pecorelli A, Grasso G, Aloisi AM, Muscettola M. Glucocorticoid receptor mRNA expression in peripheral blood mononuclear cells in high trained compared to low trained athletes and untrained subjects. J Endocrinol Invest 2009;32:816–20. [45] Fragala MS, Kraemer WJ, Mastro AM, Denegar CR, Volek JS, Kupchak BR, Häkkinen K, Anderson JM, Maresh CM. Glucocorticoid receptor expression on human B cells in response to acute heavy resistance exercise. Neuroimmunomodulation 2011;18: 156–64. [46] Boscaro M, Paoletta A, Scarpa E, Barzon L, Fusaro P, Falla F, Sonino N. Age-related changes in glucocorticoid fast feedback inhibition of adrenocorticotropin in man. J Clin Endocrinol Metab 1998;83: 1380–3.
W. Ke˛ dzierski / Journal of Equine Veterinary Science 47 (2016) 36–41 [47] Büchter D, Behre HM, Kliesch S, Chirazi A, Nieschlag E, Assmann G, von Eckardstein A. Effects of testosterone suppression in young men by the gonadotropin releasing hormone antagonist cetrorelix on plasma lipids, lipolytic enzymes, lipid transfer proteins, insulin, and leptin. Exp Clin Endocrinol Diabetes 1999;107:522–9. [48] Puder JJ, Monaco SE, Sen Gupta S, Wang J, Ferin M, Warren MP. Estrogen and exercise may be related to body fat distribution and leptin in young women. Fertil Steril 2006;86:694–9. [49] Janett F, Burkhardt C, Burger D, Imboden I, Hässig M, Thun R. Influence of repeated treadmill exercise on quality and freezability of stallion semen. Theriogenology 2006;65:1737–49. [50] Ke˛ dzierski W, Kowalik S. Leptin and ghrelin and the indices of lipid metabolism as related to sex steroid hormones in trotters. J Equine Vet Sci 2009;29:17–23. [51] Mácajová M, Lamosová D, Zeman M. Role of leptin in farm animals: a review. J Vet Med a Physiol Pathol Clin Med 2004;51:157–66. [52] Skalkidou A, Sylvén SM, Papadopoulos FC, Olovsson M, Larsson A, Sundström-Poromaa I. Risk of postpartum depression in association with serum leptin and interleukin-6 levels at delivery: a nested case-control study within the UPPSAT cohort. Psychoneuroendocrinology 2009;34:1329–37. [53] Kalbe C, Puppe B. Long-term cognitive enrichment affects opioid receptor expression in the amygdala of domestic pigs. Genes Brain Behav 2010;9:75–83. [54] Wickham SL, Collins T, Barnes AL, Miller DW, Beatty DT, Stockman CA, Blache D, Wemelsfelder F, Fleming PA. Validating the use of qualitative behavioral assessment as a measure of the welfare of sheep during transport. J Appl Anim Welf Sci 2015;18: 169–86. [55] Kulu S, Canpolat S, Aydin M, Yasar A, Tuzcu M, Baydas G. Exogenous leptin increases lipid peroxidation in the mouse brain. Tohoku J Exp Med 2005;206:233–6. [56] Horoz M, Aslan M, Koylu AO, Bolukbas C, Bolukbas FF, Selek S, Erel O. The relationship between leptin level and oxidative status parameters in hemodialysis patients. Artif Organs 2009;33:81–5. [57] Habib SA, Saad EA, Elsharkawy AA, Attia ZR. Pro-inflamatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with
[58]
[59]
[60]
[61]
[62]
[63]
[64]
[65]
[66]
41
obesity in Egyptian non-diabetic obese children and adolescents. Adv Med Sci 2015;60:179–85. Zwirska-Korczala K, Adamczyk-Sowa M, Sowa P, Pilc K, Suchanek R, Pierzchala K, Namyslowski G, Misiolek M, Sodowski K, Kato I, Kuwahara A, Zabielski R. Role of leptin, ghrelin, angiotensyn II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism. J Physiol Pharmacol 2007;58(Suppl 1):53–64. Bułdak RJ, Pilc-Gumuła K, Bułdak Ł, Witkowska D, Kukla M, Polaniak R, Zwirska-Korczala K. Effects of ghrelin, leptin and melatonin on the levels of reactive oxygen species, antioxidant enzyme activity and viability of the HCT 116 human colorectal carcinoma cell line. Mol Med Rep 2015;12:2275–82. Bilbao MG, Di Yorio MP, Galarza RA, Varone CL, Faletti AG. Regulation of the ovarian oxidative status by leptin during the ovulatory process in rats. Reproduction 2015;149:357–66. Samuel-Mendelsohn S, Inbar M, Weiss-Messer E, Niv-Spector L, Gertel A, Barkey RJ. Leptin signaling and apoptotic effects in human prostate cancer cell lines. Prostate 2011;71:929–45. Dogan S, Hu X, Zhang Y, Maihle NJ, Grande JP, Clearly MP. Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-alpha mice. Breast Cancer Res 2007;9:R91. Ray A, Nkhata KJ, Cleary MP. Effects of leptin on human breast cancer cell lines in relationship to estrogen receptor and HER2 status. Int J Oncol 2007;30:1499–509. Fiorio E, Mercanti A, Terrasi M, Micciolo R, Remo A, Auriemma A, Molino A, Parolin V, Di Stefano B, Bonetti F, Giordano A, Cetto GL, Surmacz E. Leptin/HER2 crosstalk in brest cancer: in vitro study and preliminary in vivo analysis. BMC Cancer 2008;8:305. Karaduman M, Bilici A, Ozet A, Sengul A, Musabak U, Alomeroglu M. Tissue leptin levels in patients with breast cancer. J BUON 2010;15: 369–72. Karim S, Merdar A, Achulten HJ, Jayapal M, Dallol A, Buhmeida A, Al-Thubaity F, Mirza Z, Gari MA, Chaudhary AG, Abuzenadah AM, Al-Qahtani MH. Low expression of leptin and its association with breast cancer: a transcriptomic study. Oncol Rep 2016;36:43–8.