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LifeStart sets life performance
Leonel Leal Researcher at Nutreco’s RRC
2014
Summary
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I. Metabolic programming – a new perspective on evolution?
II. Mother nature knows best – across species examples
III. Programming the pre-ruminant calf – production data
IV. Nutreco’s research program – moving forward
I. Metabolic programming
Phenotype = Genotype + Environment
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I. Metabolic programming
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“… early adaptation to a stress or stimulus that permanently change the physiology and metabolism of the organism and continue to be expressed even in the absence of the stimulus/stress that initiated them …” (Patel and Srinivansan, 2002).
II. Mother nature knows best i. The “silver spoon”effect
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Queen and workers share their genome (genetic clones)
From the larvae stage, the queen is fed royal
jelly and 10x more food then workers
Rapid growth (200mg vs. 100mg)
Longer life span (3years vs. 2mths)
Maturation of its reproductive organs
which allow the queen to lay up to 2000
eggs per day
(Maleszka, 2008; Lyko et al., 2010)
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100% of requirement
100% of requirement
100% of requirement
50%
50%
30 110 147
Control
Early restriction
Late restriction
0
20
40
60
80
100
120
Insu
lin s
ecre
tion
Control Laterestriction
0
100
200
300
400
500
600
Adi
pose
tiss
ue
mas
s
Control Laterestriction
peripheral adipose tissuecentral adipose tissue No differences of birth weights
After 1 yr, late restriction group: - Increased insulin secretion - Glucose intolerance - Increased fat mass
(Gardner et al., 2005)
II. Mother nature knows best iii. Pre-natal in sheep
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Milk formula via intragastric cannula Control : 8% CHO, 24% CP, 68% fat
High carbohydrate : 56% CHO, 24% CP 20% fat
Trial period 21 days
Hyperinsulinemia after 24h
Increased insulin levels (d12, d100)
Increased number of Langerhans-
islets (lifelong)
(Srinivasan et al., 2003)
II. Mother nature knows best iv. Post-natal in rats
III. Programming of the pre-ruminant calf
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“…conventional calf-rearing systems have restricted the amount of milk or milk replacer fed during the first weeks of a calf life in an effort to encourage solid feed intake and allow early weaning…”
(Jasper and Weary, 2002)
Poor pre-weaning diet Lower milk production
Increased milk production Enhanced pre-weaning diet
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2 L 4 L n 37 31 ADG, kg 0.80 1.03 Age at conception, (months) 14.0 13.5 Survival through 2nd lact., (%) 75.7 87.1 Milk yield through 2nd lact., (kg) 16,015 17,042
(Faber et al., 2005)
III. Programming of the pre-ruminant calf i. Colostrum
Inadaquate colostrum intake reduces lifetime production
2 L colostrum 4 L colostrum
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>12% BW
III. Programming of the pre-ruminant calf ii. Milk feeding
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III. Programming of the pre-ruminant calf ii. Milk feeding Study Milk yield difference, kg
Foldager and Krohn, 1991 1405s Foldager et al., 1997 519t Bar-Peled et al., 1998 453t Ballard et al., 2005 700s Shamay et al., 2005 981s Drackley et al., 2007 835s Raith-Knight et al., 2009 718ns Terre et al., 2009 624ns Morrison et al., 2009 0ns Moallem et al., 2010 732s Davis-Rincker et al., 2011 461ns Soberon et al., 2012 552s
| 13 (Soberon et al., 2009)
Effect continued during 2nd and 3rd lactation
0.00
0.20
0.40
0.60
0.80
1.00
1.20
1st 2nd 3rd
extr
a kg
milk
Lactation
Extra kg milk by each additional g ADG
III. Programming of the pre-ruminant calf iii. Pre-weaning growth
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LL = Low growth week 2-14 LH = Low growth week 2-8, high growth week 8-14 HL = High growth week 2-8, low growth week 8-14 HH = High growth week 2-14
** P<0.01, * P<0.05
(Brown et al., 2005)
III. Programming of the pre-ruminant calf iv. Window of opportunity
15 (Soberon et al., 2009)
Control Enhanced P value Birth weight, kg 39.2 39.7 0.90 Harvest weight, kg 61.0 83.2 < 0.01 Age at harvest, days 54.3 54.0 0.80 ADG, kg 0.39 0.82 < 0.01 Daily milk replacer intake, kg 0.6 1.3 < 0.01 Mcals above maintenance, Mcals 0.89 3.75 < 0.01
Control = 32.6 kg MR Enhanced = 69.5 kg MR
III. Programming of the pre-ruminant calf iv. Window of opportunity
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Control Enhanced P value Pancreas, g 32.90 29.47 0.61 Pancreas, % of BW 0.06 0.04 0.11 Liver, kg 1.35 2.35 < 0.01 Liver, % of BW 2.23 2.84 < 0.01 Kidney, g 183.60 319.72 0.02 Kidney, % of BW 0.30 0.38 0.09 Mammary gland, g 75.48 337.58 < 0.01 Parenchyma, g 1.10 6.48 < 0.01 Parenchyma, % of BW 0.002 0.008 < 0.01
(Soberon et al., 2009)
There are periods in life where nutrition can ‘program’ later performance responses Metabolic programming
Metabolic programming occurs in several species
Early life under-nutrition has lifelong negative effects on metabolic health
In calves, growth rates in the first 2 months have an effect on future milk production
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III. Programming of the pre-ruminant calf v. Take home messages
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Cornell &WUR microarrays
Experiment in beef animals
Experiment in dairy heifers
MODE OF ACTION
Current knowledge
IV. Nutreco’s research program – moving forward
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Control Enhanced P value ADG, kg 0.39 0.82 < 0.01 Pancreas, g 32.90 29.47 0.61 Liver, kg 1.35 2.35 < 0.01 Kidney, g 183.60 319.72 0.02 Mammary gland, g 75.48 337.58 < 0.01 Parenchyma, g 1.10 6.48 < 0.01
(Soberon et al., 2009)
IV. Nutreco’s research program i. Cornell & WUR microarrays
Control = 32.6 kg MR Enhanced = 69.5 kg MR
Micro-arrays in: Mammary gland Muscle Liver Pancreas Bone marrow Fat
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IV. Nutreco’s research program i. Cornell & WUR microarrays
Aim : Gain insight into the underlying mechanisms of differently expressed genes in tissues of pre-weaned calves (study of Soberon et al., 2009)
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IV. Nutreco’s research program ii. Beef experiment
Control = 25.3 kg MR Enhanced = 49.6 kg MR
Start
2 weeks 32 weeks 8 weeks 14 weeks
Slaughter (n=24) IVGTT (n=24)
IVGTT (n=24) Slaughter (n=60)
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MEASUREMENTS (until 32 wks)
(1) Growth performance and efficiency
(2) Glucose and insulin metabolism (IVGTT)
(3) Carcass traits and organs development
(4) Micro Arrays on tissues (muscle, pancreas and liver)
IV. Nutreco’s research program ii. Beef experiment
Aim : We hypothesize that the nutritional level imposed before weaning can affect the connectivity and function of pathways regulating energy homeostasis leading to: - Changes in the level of protein deposition and adiposity; - Carry over effects on later feedlot performance;
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Aim : We hypothesized that metabolomics will allow us to differentiate the pathways that are altered by nutrition early in life that can impact later life productivity
I. Discover/identify bio-markers that can allow us to link early nutrition effects with increased life performance;
II. Study the glucose metabolism of calves pre- and post weaning in enhanced CMR feeding regimes (insulin resistance);
IV. Nutreco’s research program iii. Metabolomics in dairy heifers
Control = 25.3 kg MR Enhanced = 49.6 kg MR
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2 3 4
DEVELOPMENT MILESTONES:
1 Milk-phase: Jan 2014 - Dec 2014
2 1st Insemination: Feb 2015 - Jan 2016
3 1st Lactation: Nov 2015 - Oct 2016
4 2nd Lactation: Jan 2017- Dec 2017
5 End: DEC 2018
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IV. Nutreco’s research program iii. Metabolomics in dairy heifers
