Leptin in sow: Influence on the resumption of cycle activity after weaning and on the piglet gain

Livestock Science 124 (2009) 107–111 Contents lists available at ScienceDirect Livestock Science j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / l i v s c i Leptin in sow: Influence on the resumption of cycle activity after weaning and on the piglet gain A. Summer ⁎, R. Saleri, M. Malacarne, S. Bussolati, V. Beretti, A. Sabbioni, P. Superchi Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti, Università degli Studi di Parma, 43100 Parma, Italy a r t i c l e i n f o Article history: Received 22 August 2008 Received in revised form 12 January 2009 Accepted 13 January 2009 Keywords: Leptin Sow Cycle resumption Piglet growth a b s t r a c t In sows, a strong relationship exists between body condition and reproductive efficiency and milk yield. Leptin may act as a metabolic gate which permits the activation of reproductive axis: in the sow, serum concentration of leptin was positively correlated with adiposity at farrowing. An interesting aspect useful to clarify the biology of leptin, was the discovery that the placenta expresses the ob gene, the ob receptor gene and it is a site of leptin production, suggesting a possible role of the hormone in fetal growth; after birth, the placenta functions were taken over from milk, especially to the delivery of maternal hormones and growth factors to the neonate. The exact role of maternal leptin in the physiology of neonatal piglets remains to be determined. Our aim was to evaluate if maternal leptin levels at the beginning of lactation and at weaning could predict the resumption of cycle activity and/or the piglet gain. Thirty-eight Large White × Landrace pregnant sows (16 nulliparous and 22 pluriparous) were used. Blood samples were taken from sows and piglets at d 5 and d 21 after farrowing; in the same days, milk samples were taken after oxytocin injection by means of complete manual milking of all mammary glands of one side. On the basis of the blood leptin at d 5, sows were divided into 3 groups (Low: b 2.3 ng/ml; Medium: 2.3 to 2.6 ng/ml; High: N 2.6 ng/ml). Our results show a correlation at d 5 between backfat thickness and blood leptin (r = 0.342; P b 0.05). The resumption of the cyclic activity was faster in sows with a leptin level at d 5 greater than 2.3 ng/ml (P b 0.01). Milk composition at d 5 and 21 was not affected by parity and leptin. Piglet ADG was significantly (P b 0.05) influenced by sow leptin groups (0.180 kg day− 1 for piglets from Low group and 0.224 for High group). Piglets weaned by High group sows have shown a greater blood leptin content at weaning (P b 0.01) than other groups. In conclusion we have found a significant correlation between leptin and productive and reproductive performances of pigs. This paper underlines the pleiotropic actions exerted by leptin in the productive sow. © 2009 Elsevier B.V. All rights reserved. 1. Introduction In modern high-producing herds, the maintenance of an optimal body condition of sows is a prerequisite to achieve adequate production levels. In the sow, a strong relationship exists between body condition and reproductive efficiency ⁎ Corresponding author. Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti, Università degli Studi di Parma, strada del Taglio 10, 43100 Parma, Italy. Tel.: +39 0521032613; fax: +39 0521032611. E-mail address: andrea.summer@unipr.it (A. Summer). 1871-1413/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.livsci.2009.01.005 (Mullan and Williams, 1989; van der Peet-Schwering et al., 1998, Hultén et al., 2002, Maes et al., 2004). Body reserves are also determinants of milk yield. Pulske and Dong (1998) show that the metabolic state of sows during lactation influences the milk dry matter conversion in piglet gain. Sows in good condition produced more milk, energy and protein than thin sows (Klaver et al., 1981). In early lactation, sow body composition affected milk production and only during the progression of lactation the dietary intake of precursors for milk synthesis becomes more important (Revell et al., 1998). Lactation is a complex, and unique physiological state characterized by behavioral and neuroendocrine adaptations which shift the energy balance to milk components synthesis. A 108 A. Summer et al. / Livestock Science 124 (2009) 107–111 variety of hormones and metabolic signals modulates the body omeostasis by regulating the food intake/energy balance; in particular, the hypothesis that adipose tissue is the source of hormones controlling metabolism is not new (Kennedy, 1953). The discovery of obese gene and its product, leptin, by Zhang et al. (1994) supported this concept. Leptin is mainly produced by adipocytes and adipose and blood leptin levels are coupled to energy stores. Serum leptin concentrations have been demonstrated to be positively correlated with adiposity of sows at farrowing and inversely related to feed intake during lactation (Estienne et al., 2000). Barb and Kraeling (2004) showed a strong link between leptin, luteinizing hormone (LH) and growth hormone (GH). In sows plasma leptin is associated with backfat depth and the loss of backfat depth during lactation is associated with reproductive performance (De Rensis et al., 2005). However, there is not a direct association between plasma leptin and reproductive performance. An interesting aspect useful to clarify leptin biology, was the discovery that placenta expresses both ob and ob receptor gene and it is a site of leptin production (Smith-Kirwin et al.,1998), thus suggesting a possible role of the hormone in fetal growth; after birth, placenta functions are taken over from milk, especially to deliver maternal hormones and growth factors to the neonate. In the sow, leptin concentrations in whole milk are much greater than blood ones and reflect dietary energy intake during pregnancy (Estienne et al., 2003; Woliński et al., 2003). The presence of leptin in human milk raised the possibility that maternal leptin may exert biological effects on the infant at a time in which both adipose tissue and the appetite regulatory systems are immature (Casabiell et al., 1997). Our aim was to evaluate if maternal leptin levels, determined 5 d after farrowing and at weaning could predict the resumption of cycle activity and/or the piglet gain. We chose to take the first blood and milk sample 5 days after the delivery to reduce the effects of hormonal changes at the farrowing on leptin levels and because at 5 d, the colostrum secretion was replaced by milk secretion. 2. Materials and methods 2.1. Experimental groups Thirty-eight Large White × Landrace sows (16 nulliparous and 22 pluriparous) were randomly selected from the herd effective in the same reproduction status during two months. Mean (±SD) parity order of pluriparous sows was: 3.22 ± 0.75. All sows received, from d 7 to d 35 of gestation, a complete feed (13.95% crude protein, 2803 kcal ME/kg, 0.65% lys as-fed basis) in different amounts to obtain a final BCS value of 3.5. The amount of the same complete feed was 2.8 kg head− 1 d− 1 from d 36 of gestation to farrowing. During lactation feed (15.60% crude protein, 2832 kcal ME/kg, 0.92% lys as-fed basis) was offered ad libitum; the mean intake during lactation was 4.7 kg head− 1 d− 1. During both gestation and lactation free access to water was provided. At d 110 of gestation sows entered the farrowing room; they were evaluated for fat thickness at P2 level using an amode ultrasound (Lean-meater, Renco Corporation, Minneapolis, MN, USA); the measurement was repeated at the end of lactation (21 d). After weaning, the sows were kept in individual cages until successive pregnancy control. Blood samples from jugular vein were taken from sows and piglets 5 (+5 d) and 21 d (+21 d) after farrowing; in the same days, milk samples were taken after oxytocin injection (30 IU in auricular vein) by means of complete manual milking of all mammary glands of one side. On the basis percentile frequency (33%) of blood leptin concentrations 5 d after farrowing, sows were divided into 3 groups (Low: b2.3 ng/ml — parity 2.50 ± 1.29; Medium: 2.3 to 2.6 ng/ml — parity 2.50 ± 1.29; High: N2.6 ng/ml — parity 2.17 ± 1.34). In Low group (n.13) 36% were nulliparous and 64% pluriparous, as in Medium (n.13) and High (n.12) the ratio was 50/50 and 42/58, respectively. The number of piglets born alive, stillborn and weaned was recorded, as well as their weight at litter balancing (within 24 h from farrowing) and at weaning. Litter balancing was carried out by assigning 9–10 piglets to each nulliparous and 10–11 to pluriparous. Milk production was estimated on the basis of litter growth, according to the equation proposed by Noblet and Etienne (1989). The weaning-to-estrus interval (WOI) and number of service per conception were recorded. 2.2. Analytical methods Serum samples were obtained by centrifugation at 536 g for 10 min and were kept at − 20 °C until analysis; milk samples were treated as suggested by Estienne et al. (2000). In particular, skimmed milk was obtained by heating whole milk until 40 °C for 10 min, then centrifuged at 1489 g for 10 min; fat was removed by a vacuum pump. Leptin content in blood and milk was determined by a commercial kit (Multi species Leptin RIA — Linco Research, St. Louis, MO), previously validated in swine for serum (Qian Table 1 Full cream milk composition. Item Milk composition at d 5 Fat Protein Lactose Milk composition at d 21 Fat Protein Lactose Leptin group a Parity Nulliparous (no. 16) Pluriparous (no. 22) Low (no. 13) Medium (no. 13) High (no. 12) 9.67 ± 0.48 5.42 ± 0.18 4.56 ± 0.13 10.26 ± 0.39 5.55 ± 0.14 4.52 ± 0.11 9.73 ± 0.57 5.58 ± 0.21 4.63 ± 0.16 9.87 ± 0.49 5.40 ± 0.18 4.47 ± 0.14 10.28 ± 0.53 5.48 ± 0.20 4.52 ± 0.15 8.41 ± 0.65 4.84 ± 0.18 4.57 ± 0.17 9.36 ± 0.53 5.05 ± 0.14 4.65 ± 0.14 8.78 ± 0.78 4.85 ± 0.21 4.60 ± 0.21 8.76 ± 0.67 4.93 ± 0.18 4.72 ± 0.18 9.12 ± 0.73 5.05 ± 0.20 4.52 ± 0.19 Least squares means ± SE, g/100 g. a Low: b2.3 ng/ml; Medium: 2.3 to 2.6 ng/ml; High: N2.6 ng/ml. 109 A. Summer et al. / Livestock Science 124 (2009) 107–111 Table 2 Sows and piglets performance. Item Backfat Farrowing, mm Weaning, mm Loss, mm Sows with WEI b b 7d, % Service/conception, no. Milk yield, kg/d Piglets born alive, no. Piglets at 21d, no. Piglets weight 21d, kg ADG, kg/d Leptin group a Parity Nulliparous (no. 16) Pluriparous (no. 22) Low (no. 13) Medium (no. 13) High (no. 12) 22.59 ± 1.19 17.71 ± 0.96 4.88 ± 0.64 56.3A 1.92 ± 0.21b 5.47 ± 0.24A 8.02 ± 1.04 9.36 ± 0.12A 5.52 ± 0.18a 0.184 ± 0.007A 21.95 ± 0.97 17.49 ± 0.78 4.45 ± 0.52 90.9B 1.24 ± 0.17a 6.86 ± 0.20B 10.19 ± 0.86 9.82 ± 0.10B 6.15 ± 0.15b 0.224 ± 0.006B 20.88 ± 1.43 16.32 ± 1.15 4.55 ± 0.76 45.5A 2.36 ± 0.25B 6.23 ± 0.29 9.50 ± 1.26 9.73 ± 0.15 5.72 ± 0.20 0.180 ± 0.008a 22.48 ± 1.23 18.23 ± 0.99 4.25 ± 0.66 92.9C 1.08 ± 0.21A 6.13 ± 0.25 9.40 ± 1.08 9.54 ± 0.13 5.96 ± 0.18 0.209 ± 0.008b 23.46 ± 1.33 18.26 ± 1.07 5.20 ± 0.71 83.3B 1.30 ± 0.23A 6.14 ± 0.27 8.41 ± 1.17 9.50 ± 0.14 5.81 ± 0.19 0.224 ± 0.008c a,b,c Least square means in the same row and source of variations (parity or leptin group) without a common superscript differ (P b 0.05). Least square means in the same row and source of variations (parity or leptin group) without a common superscript differ (P b 0.01). Least squares means ± SE. a Low: b2.3 ng/ml; Medium: 2.3 to 2.6 ng/ml; High: N2.6 ng/ml. b WEI = interval from weaning to estrus. A,B,C et al., 1999) and milk (Estienne et al., 2000). The sensitivity of the method was 100 pg/tube and variability coefficients within and among samples were 4.2% and 7.1%, respectively. Chemical composition of full cream milk (protein, fat, lactose) was performed by near infrared analysis with Milk-oScan 134 A/B (Biggs, 1978) and data are summarized in Table 1. 2.3. Statistical analysis Productive and reproductive data were analyzed by twoway ANOVA (SAS Inst. Inc., Cary, NC), with parity (nulliparous, pluriparous) and leptin group (Low, Medium, High) as fixed factors and interaction. Moreover, milk composition, leptin content, backfat thickness and litter parameters at d 21 were covaried with respective values at d 5. Pearson correlation coefficients were obtained by residual analysis, after the application of the ANOVA model. Non parametric data were analyzed by χ2 test. 3. Results Productive and reproductive sow parameters were showed in Table 2. Sows were divided into three groups on the basis of blood leptin levels at + 5 d: Low (b2.3 ng/ml; n = 13), Medium (from 2.3 to 2.6 ng/ml: n = 13) and High (N2.6 ng/ ml; n = 12). Interaction between parity and leptin group was not significant. Backfat thickness in nulliparous and pluriparous sows at +5 d was 22.59 ± 1.19 mm and 21.95 ±0.97 mm, respectively. Backfat thickness at farrowing was correlated to blood leptin content at +5 d (r = 0.342; P b 0.05), while at weaning the correlation was not significant. Backfat thickness loss at weaning was similar in relation to parity and leptin group (Table 2). The resumption of cyclic activity was faster in pluriparous than in nulliparous sows, and in sows with a leptin level at +5 d greater than 2.3 ng/ml (P b 0.01). Only 45.5% of sows of Low group showed a heat within d 7 from weaning. For these sows the number of services per conception was greater (2.36) than that of other groups (Medium = 1.08, High = 1.30; P b 0.01). Pluriparous sows produced 25% more milk than nulliparous ones (P b 0.01). Milk composition 5 and 21 d after farrowing was not affected by parity and leptin group (Table 1); the greater milk nutrient intake of piglets from pluriparous sow has determined a greater ADG (Table 2). The ADG showed by piglets, was also affected (P b 0.05) by leptin class of sows (0.180 kg day− 1 for piglets from Low group and Table 3 Concentrations of leptin in serum and skim milk. Item Piglets serum At 5 d At weaning Sows serum At 5 d At weaning Sows skim milk At 5 d At weaning a,b Leptin group a Parity Nulliparous (no. 16) Pluriparous (no. 22) Low (no. 13) Medium (no. 13) High (no. 12) 3.29 ± 0.21 2.29 ± 0.25 3.42 ± 0.17 2.65 ± 0.24 3.07 ± 0.25 2.37 ± 0.34A 3.23 ± 0.21 1.77 ± 0.27A 3.76 ± 0.24 3.27 ± 0.29B 2.53 ± 0.10 2.39 ± 0.10 2.59 ± 0.08 2.39 ± 0.08 2.03 ± 0.12A 2.28 ± 0.11a 2.42 ± 0.10B 2.29 ± 0.10a 3.23 ± 0.11C 2.61 ± 0.11b 6.23 ± 0.14 6.34 ± 0.11 6.46 ± 0.11 6.30 ± 0.08 6.34 ± 0.17 6.37 ± 0.13 6.25 ± 0.14 6.24 ± 0.10 6.43 ± 0.15 6.36 ± 0.11 Least square means in the same row without a common superscript differ (P b 0.05). Least square means in the same row without a common superscript differ (P b 0.01). Least squares means ± SE, ng/ml. a Low: b2.3 ng/ml; Medium: 2.3 to 2.6 ng/ml; High: N2.6 ng/ml. A,B,C 110 A. Summer et al. / Livestock Science 124 (2009) 107–111 0.224 for High group). Piglet weight at weaning was not significantly affected by leptin group (P N 0.05). Blood leptin content of piglets at d 5 (Table 3) was not correlated to leptin content in milk and it was not affected by parity and leptin group (P N 0.05). At weaning piglets by High group presented a greater blood leptin concentration (P b 0.01) than other groups. After 21 day of lactation the blood leptin concentration is higher for High group sows (P b 0.05). Skimmed milk leptin content (mean±SD) at +5 d and +21 d was 6.34±0.15 ng/ml and 6.32 ± 0.13 ng/ml, respectively: no differences were observed in relation to parity or sows group. 4. Discussion Adipocytes play a dynamic role in body homeostasis and in the regulation of energy expenditure, according to several factors, such as feeding behavior, hormones and growth factors. Leptin, an adipokyne mainly produced by adipocytes, is a key metabolic signal to the brain, reflecting both energy stores and energy balance. Leptin acting at the brain to increase energy expenditure and alter endocrine activity has been previously reported in the pig (Barb et al., 2002). This hormone is implicated in the reproductive process as well as in glucose and lipid metabolism (Bamshad et al., 1999; Barb et al., 2002). It is well established that reproduction is very sensitive to nutritional status and that metabolic state, in particular energy balance, is a potent regulator of leptin secretion and gene expression in pigs (Spurlock et al., 1998; Barb et al., 2001). Mechanisms regulating energy balance are considered sensitive to metabolic signals generated by changes in oxidation of metabolic fuels and could account for positive correlations between body fat, fertility and endocrine function (Barb et al., 1997). In our study backfat depths at farrowing and at the end of lactation appeared adequate to energy demand due to milk production (Whittemore and Morgan, 1990; Whittemore, 1996; Dourmad et al., 2001). Maes et al. (2004) reported that backfat variations at weaning were greater when no piglets were transferred from one sow to another during the first 3 d of lactation. In our study all litters were balanced within 24 h: we may think that this is important for a reduced variation of thickness in sows. However, we observed, as previously reported by others (Barb, 1999; Estienne et al., 2000; De Rensis et al., 2005) a link between blood leptin level and backfat thickness. The mechanisms controlling energy intake, storage and expenditure are fundamental to answer the fluctuations of body during the day and also in particular metabolic condition, i.e. lactation. We also observed a clear and strong leptin involvement in reproduction regulation, in particular in relation to the resumption of the cyclical activity after delivery. We have found, in fact, an increase of the interval farrowing — estrus in all the animals, irrespective of parity order, in the presence of low leptin blood concentrations. Leptin role in reproduction remains controversial: many studies show that leptin acts as a permissive signal to trigger puberty and to resume reproductive function (Apter, 1997; Cheung et al., 1997; Schneider and Zhou, 1999). The presence of the long form leptin receptor in both hypothalamus and pituitary (Lin et al., 2000) and the leptin-induced LH secretion from pig pituitary cells and GnRH release from hypothalamic tissue in vitro (Barb and Kraeling, 2004), suggest that leptin acts through the hypothalamic–pituitary axis. A recent study demonstrated that metabolic signals are communicated, at least in part, to GnRH neurons via the γ-aminobutyric acid neuronal pathway (Sullivan and Moenter, 2004). However, maternal leptin role in the neonate piglets remains to be fully established. Our data indicate that there are no differences in leptin concentrations in piglets 5 d after birth, even if average daily gain is significantly related to maternal plasma leptin. As milk production and composition were not affected, in our study, by maternal leptinemia, we may hypothesize that all piglets received the same amount of nutrients. A role for leptin in maternal milk has yet to be defined, the presence of leptin in milk suggests a possible biological importance of leptin on the neonatal piglets, especially on the gastrointestinal tract, because epidermal growth factor in milk has been shown to stimulate the intestinal development (Woliński et al., 2003). Sows in our study show low leptin concentration in milk, as reported also by other authors (Estienne et al., 2000). However, according to Estienne et al. (2000), we found the same trend of the hormone during lactation: leptin remains constant as lactation proceeds and it is not influenced by parity and blood leptin group. In this context, we remind also that leptin is a part of the cytokine cascade, which orchestrates the innate immune response and host defense mechanisms. Local leptin secretion may play an important role, as a metabolic factor, in the distribution of nutrients and in energy partitioning in the mammary gland during lactation, as demonstrated by Feuermann et al. (2004), in the cow. 5. Conclusions The presence of low leptin blood concentrations is correlated to an increase of the interval farrowing — estrus in all the animals, irrespective of parity order. Differences were not evidenced in leptin concentrations in piglets 5 d after birth, even if average daily gain is significantly related to maternal plasma leptin. The milk production and composition seem not to be affected by maternal leptinemia. In this study leptin remains constant as lactation proceeds and it is not influenced by parity and blood leptin group. 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