The metabolic status of the lactating sow. Consequences on milk production and post- weaning reproduction response.

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1 nutrition-reproduction interactions in the breeding sow The metabolic status of the lactating sow. Consequences on milk production and post- weaning reproduction response. Marie-Christine Père UMR SENAH, Saint-Gilles, France

2 The metabolic status of the lactating sow Mammary uptake of nutrients during lactation Insulin resistance Metabolic status of the lactating sow and milk production Metabolic status of the lactating sow and reproduction

3 Evolution of the rythm of reproduction of sows W FI - Lactatio on duration Year Nb litter rs/year Age at weaning Weaning- Fecundation Interval Litters/year Dourmad, according to

4 Evolution of sow prolificacy itter Piglets/l total born born alive weaned losses Losses (% %) Year Dourmad, according to

5 Evolution of sow prolificacy itter Piglets/l total born born alive weaned losses Losses (% %) Year Dourmad, according to

6 Evolution of sow productivity and longevity Piglets weaned / sow at culling 55 Age at culling, months 5.5 Age at cull ing (months s) Piglets weaned / sow Litters / sow culled Litter rs / sow Year Dourmad, according to

7 Litter size and milk production milk produc ction, kg/ /d Elsley, 1971 Auldist et al., 1994 King et al., litter size Etienne et al., 2000

8 Litter size and milk production milk produc ction, kg/ /d Elsley, 1971 Auldist et al., 1994 King et al., litter size Etienne et al., 2000

9 Litter size and milk production milk produc ction, kg/ /d Elsley, 1971 Auldist et al., 1994 King et al., litter size Etienne et al., 2000

10 productivity i requirements for milk production weight of adult sows maintenance requirements appetite has not in proportion increased importance of mobilizable body fat and protein reserves during lactation

11 Milk production Milk production has priority over body reserves But, important or prolonged nutrient deficiency can affect milk production further reproductive traits Metabolic and physiological adaptations are necessary to preferentially e e ta drive nutrients ts towards udder

12 The metabolic status of the lactating sow Mammary uptake of nutrients during lactation Insulin resistance Metabolic status of the lactating sow and milk production Metabolic status of the lactating sow and reproduction

13 Mammary uptake of nutrients during lactation AA GLU TGly Gly Amino Acid Glucose NEFA αgp Tissue Protein Milk Protein Milk Lactose Milk Fat O 2 NADH,NADPH CO 2 Mammary Glands

14 Mammary uptake of nutrients during lactation AA GLU TGly Gly Amino Acid Glucose NEFA αgp Tissue Protein Milk Protein Milk Lactose Milk Fat O 2 NADH,NADPH CO 2 Mammary Glands

15 Mammary uptake of nutrients during lactation AA GLU TGly Gly Amino Acid Glucose NEFA αgp Tissue Protein Milk Protein Milk Lactose Milk Fat O 2 NADH,NADPH CO 2 Mammary Glands

16 Partition of energy uptake by mammary glands (from Farmer et al., 2008) a kj/l plasm Energ gy uptake, Amino acids NEFA Triglycerides Lactate Glucose post-prandial p fasted restrictively fed (Dourmad et al., 2000) (Renaudeau et al., 2002)

17 Partition of energy uptake by mammary glands (from Farmer et al., 2008) a kj/l plasm Energ gy uptake, Amino acids NEFA Triglycerides Lactate Glucose post-prandial p fasted restrictively fed (Dourmad et al., 2000) (Renaudeau et al., 2002)

18 The metabolic status of the lactating sow Mammary uptake of nutrients during lactation Insulin resistance Metabolic status of the lactating sow and milk production Metabolic status of the lactating sow and reproduction

19 Insulin resistance High glucose requirements - for foetal growth in late pregnancy - for milk production physiological and metabolic adaptations of the sow are necessary 2 experiments: - effect of pregnancy (pregnant vs. non pregnant) - effect of the physiological stage (mid and late pregnancy, lactation, post-weaning

20 Insulin resistance : methodology 1/ Meal test Same (amount, composition) standard meal fed at different physiological stages (G, L, PW) Serial blood samplings : before the meal and during 4h after feeding. Pre post prandial kinetics of blood concentrations of glucose, insulin, NEFA,

21 Meal test during pregnancy 300 P NP FFA (µmol/ /L) day 30 to time (min) From day 30 to day 101 of gestation : FFA profiles similar in pregnant and non pregnant sows

22 Meal test during pregnancy 300 P NP 300 P NP FFA (µmol/ /L) day 30 to 101 L) FFA (µmol/ day time (min) time (min) From day 30 to day 101 of gestation : FFA profiles similar in pregnant and non pregnant sows At day 108 of gestation : basal and post feeding FFA in pregnant sows > non pregnant sows

23 Meal test, NEFA MP EP L PW NEFA, µm time, min (t0 = meal) Before and after meal intake: NEFA in lactation > other stages

24 Meal test, glucose se, mm Gluco 10 MP EP L PW time, min (t0 = meal) Fasting : Lactation < others stages Post prandial : Lactation > others stages

25 Meal test, insulin µu/ml Insulin, MP EP L PW time, min (t0 = meal) area under insulin curve : lactation > other stages

26 Meal test, insulin µu/ml Insulin, MP EP L PW area under insulin curve and postprandial glycemia : lactation > other stages, mm Glucose time, min (t0 = meal) MP EP L PW time, min (t0 = meal)

27 Insulin resistance : methodology 2/ Glucose tolerance test Infusion of glucose (0.5 g/kg BW) via a jugular catheter. Serial blood samplings via a carotid catheter : before and during 90 min after infusion. i Pre post infusion kinetics of blood concentrations of glucose, insulin, NEFA, Calculation of glucose half-life

28 Glucose tolerance at 108 days of gestation Glu lucose (mmol/ l/l) 35 P NP NP time time (min) (min) decrease of plasma glucose is slower in pregnant than in non pregnant sows

29 Glucose tolerance at 108 days of gestation Glu lucose (mmol/ l/l) 35 P NP NP time time (min) (min) In nsulin (µu/ml L) 500 P NP time (min) decrease of plasma glucose is slower in pregnant than in non pregnant sows insulin area is similar in pregnant and non pregnant sows, but insulin secretion is delayed in pregnant sows

30 Glucose tolerance test MP EP L PW Glucose half-lifelife e, mm Glucos time, min (t0 = glucose injection) MP : 12.0 a EP : 14.7 b L : 22.4 c PW : 10.8 a

31 Insulin resistance : methodology 3/ Euglycemic hyperinsulinemic clamp Infusion of insulin at a constant rate hyperinsulinemia Simultaneous infusion of glucose at variable rate euglycemia : maintenance of basal glycemia Insulin sensitivity estimated by the amount of glucose needed to maintain the basal glycemia kinetics of blood concentrations of glucose, insulin, NEFA,

32 3/ Euglycemic hyperinsulinemic clamp

33 3/ Euglycemic hyperinsulinemic clamp

34 3/ Euglycemic hyperinsulinemic clamp

35 3/ Euglycemic hyperinsulinemic clamp

36 3/ Euglycemic hyperinsulinemic clamp

37 Glycemia and glucose infusion rate Glucose, mm Blood MP EP L PW GIR, mg.kg -1.min glycemia maintained at the basal level glucose infusion rate (GIR) plateau from 120 min Time, min

38 Glucose infusion rate n -1 GIR, mg..kg -1.min Insulin infused, ng.kg -1.min MP EP L PW Physiological stage

39 NEFA t MP EP L PW NE EFA, % of time, min Inhibition of NEFA : PW & MP > EP > L

40 The metabolic status of the lactating sow Mammary uptake of nutrients during lactation Insulin resistance Metabolic status of the lactating sow and milk production Metabolic status of the lactating sow and reproduction

41 Oxytocin Maternal behaviour and parturition Milk production milk ejection : oxytocin burst mobilization of body reserves : oxytocin overall concentrations (Valros et al.,2004)

42 Prolactin Initiation and maintenance of milk production PRL before parturition, 2-3 weeks of lactation, ti PW PRL release related to the amount of the udder post-massage Suckling interval Milk production PRL seems to be involved in energy metabolism increased PRL level improvement of lactation performance Feed restricted : PRL in high litter weight gain sows > PRL in low litter weight gain sows redirects energy to the mammary gland rather than to sow body reserves (insulin receptors) PRL stimulates glucose metabolism in mammary tissues in vitro PRL involved in AA transfer in mammary cells However, some works do not show a relationship between normal PRL levels and indicators of body store mobilization or milk production

43 Growth hormone GH at onset lactation, high levels during 2-3 weeks of lactation, PW Catabolic activity of GH in case of nutrient deficiency GH in restrictively fed sows > in sows liberally fed GH in sows fed a protein/lysine deficient diet > sows fed a control diet GH in sows with high h litter ADG > less productive sows Positive correlation between GH level and sow weight loss High GH levels in lactation Favor drive of nutrients to the mammary glands Mobilize body fat and minimize body protein losses in the case of negative energy balance

44 Insulin like growth factor-i IGF-I after farrowing, high levels during lactation IGF-I is lower : In lactating sows fed restrictively than in sows fed ad libitum in sows fed a protein/lysine deficient diet than in sows fed a control diet uncoupling of GH and IGF-I in the case of a nutritional deficiency Uncoupling due to a hepatic resistance to GH? (Mejia-Guadarrama et al., 2002) Resistance to GH and low IGF-I facilitate protein mobilization from body reserves Positive relation ships between IGF-I level and milk protein, fat, and lactose yield (Pettigrew et al., 1993) But IGF-I seems not have a direct action on milk production (Monaco et al., 2005)

45 Insulin Fasting levels of insulin during lactation (like glucose) Low insulin glucose and AA utilization by muscle and fat tissues This favors drive of nutrients to the mammary glands Insulin in restrictively fed sows < in sows liberally fed Insulin in sows fed a protein/lysine deficient diet < sows fed a control diet Insulin in sows with high litter ADG < less productive sows But some contradictory results Insulin may be involved in AA transport in mammary glands Injections of insulin in lactating sows litter ADG in well fed sows (during early, mid, or late lactation) litter ADG in feed restricted sows (during the 4 th week)

46 Leptin High leptin level after farrowing low lactation feed intake Leptin level l after farrowing : heavy sows > light sows in fat sows > lean sows sows fed liberally in gestation > restricted sows Positive correlation between leptin level and backfat depth

47 The metabolic status of the lactating sow Mammary uptake of nutrients during lactation Insulin resistance Metabolic status of the lactating sow and milk production Metabolic status of the lactating sow and reproduction

48 Metabolic status and reproduction Central nervous system Neurotransmitters EOP Teat stimulation by suckling Hypothalamus Pituitary gland Posterior Anterior + Oxytocin LH Prl GH TSH ACTH FSH IGF-I T4,T3 Cortisol

49 Metabolic status and reproduction Nutritional deficiency during lactation = additional inhibitory factor of the reproductive axis primiparous sows high yielding sows Inhibition of frequency of LH pulses delayed return into oestrus ovulation rate quality of follicles and oocytes effects on embryonic survival and growth (Dr. G.R. Foxcroft) Recent studies on severe nutritional deficiency : only marginal delay of oestrus after weaning but ovulation of poorly mature oocytes???

50 Metabolic status and reproduction Cerebellum Forebrain Oxidizable substrates Pancreas Adipose tissue AP? Insulin Leptin? POA VMH GnRH pulses

51 Metabolic status and reproduction Positive role of glucose and insulin on LH secretion. In feed-restricted gilts : glucose administration and rise of insulin LH pulsatility. Glucose restriction LH pulse frequency Leptin and IGF-I could be involved in the prolonged lactational anoestrus Folliculogenesis could be altered by insulin and IGF-I I induced by nutritional deficiency.

52 Metabolic status and reproduction depends on body reserves, tissue mobilisation, and nutritional deficiency. interval from weaning to oestrus depends on amplitude of body reserves mobilisation body reserves at weaning. protective role of high protein reserves threshold level of losses of body reserves (16% of the lean mass at farrowing)

53 How to prevent nutritional deficiency? optimise feed intake : feeding pattern feed appetence good sanitary conditions important in summer but insufficient for good performance optimise body reserves : restore body reserves during pregnancy but avoid too fatty sows optimise litter management : cross-fostering and split weaning

54 How to prevent nutritional deficiency? manipulate diet composition energy concentration of the diet (addition of fat) generally decreases feed intake milk fat content beneficial to piglets little benefit for energy balance of the sow blood glucose/insulin : starch rich vs. fat rich diet glucose - insulin levels stimulates LH at 7 days, not thereafter no effect on weaning-oestrus interval

55 How to prevent nutritional deficiency? Delay post-weaning breeding Breeding at the 2 nd oestrus litter size 5-12 days delay of ovulation and insemination (progestagen) ovulation rate and nb foetuses at 50 days Economical interest t??

56 Conclusion Complex endocrine adaptations during lactation sustain milk synthesis feed intake nutrient storage preferential drive of nutrients mammary glands

57 Conclusion Complex endocrine adaptations during lactation sustain milk synthesis GH : lipid mobilization insulin & IGF-I : facilitate AA and lipid mobilization GH IGF-I uncoupling facilitates protein mobilization Insulin resistance : spares absorbed glucose, gluconeogenesis PRL modulated insulin receptors Oxytocin : mobilization of maternal reserves?

58 Conclusion Direct action of hormones on milk production less clear no effect of pgh in most experiments positive relationships with IGF-I and insulin? stimulation by PRL?

59 Conclusion Excessive mobilization of body reserves reproduction problems likely mediated through inhibition of GnRH secretion available metabolic substrates = 1 st signal? positive role of glucose and insulin on LH secretion role of leptin and IGF-I? effects on the quality of oocytes in recent studies

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