choline biology and nutrition in the transition dairy …...choline biology and nutrition in the...
TRANSCRIPT
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Choline biology and nutrition in the transition dairy cow
Joseph W. McFadden, Ph.D.
Assistant Professor of Dairy Cattle Biology
Northeast Agribusiness & Feed Alliance Faculty Fellow
Department of Animal Science
1Presented 1.28.20
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Talking points
➢ Transition cow biology▪ Metabolism and the need for a healthy liver
▪ Causes of fatty liver disease and ketosis
▪ Impact of poor transition cow liver health
➢ Importance of choline▪ Choline and choline metabolites
▪ Metabolism of choline
▪ How does choline enhance health?
➢ Benefits of rumen-protected choline feeding▪ Why do we need to rumen-protect choline?
▪ Benefits of rumen-protected choline feeding: Metabolism, milk, and health
▪ What can we learn from recent meta-analyses?
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Transition cows experience negative energy balance
➢ Reduced energy intake and increased
energy demands for milk
Feed energy
Milk energy
Energ
y M
cal/D
ay
Body energy stores
Days in milk
0 100 200 300
C
A
B
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The transition cow adapts to meet energy demand
➢ Coordinated changes in
metabolism support calf
development and milk production.
▪ Body fat breakdown provides
fatty acids for fuel and milk
▪ Decreased insulin secretion
▪ Decreased insulin sensitivity to
spare glucose for milk
▪ Glycogen stores are utilized
▪ Glucose and ketone synthesis
occurs in the liver
A
B
Bauman and Currie, 1980; Bell and Bauman, 1997
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A B
Drackley, 1999; Aschenbach et al., 2010
A healthy liver benefits the transition cow
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In general…
➢ High energy dry cow diets
➢ Extended dry periods
➢ High calving BCS
➢ Inadequate postpartum energy intake
➢ Increased parity
➢ Environmental stressors
6
What can cause moderate/severe fatty liver disease?
More specific…
➢ Accelerated adipose insulin
resistance and fat breakdown
➢ Elevated hepatic fatty acid uptake
➢ Inadequate fatty acid oxidation
➢ Triglyceride accumulation
➢ Inadequate very-low-density
lipoprotein secretion
Other triggers?
➢ Endotoxin?
➢ Microbiome factors?
Bobe et al., 2004
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An unhealthy liver impairs the transition cow
Veenhuizen et al., 1991; Rukkwamsuk et al., 1999; Hammon et al., 2009
➢ Increased NEFA
increases hepatic [TAG]
➢ Reduced
gluconeogenesis
➢ Greater glycogen
depletion
➢ Lower circulating
glucose
➢ Impaired milk
production
High vs. Low
Liver Fat
Low vs. High
Liver Fat
Low vs. High
Liver FatA B
C D
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Fatty liver is associated with the development of other postpartum disorders
Bobe et al., 2004
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Fatty liver impairs fertility in dairy cows
Bobe et al., 2004
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The origins of choline:Theodore Gobley, Adolph Strecker and Oscar Liebreich
10Zeisel et al., 2012
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The origins of choline: Charles Best and Fredrick Banting
11Hershey and Soskin, 1931; Zeisel et al., 2012
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Choline
➢ A quaternary ammonium and water soluble compound
➢ Considered a quasi-vitamin and methyl donor
➢ Need for neurotransmitter synthesis (i.e., acetylcholine)
➢ Precursor for complex lipid synthesis
➢ Needed for building biological membranes
➢ Need to assemble very-low-density lipoproteins
➢ Deemed essential when methyl precursors are low in diets
➢ Supplemented in diets as choline chloride
➢ Absorbed from the intestines via choline transporter-like proteins
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Choline metabolism
1313
A methyl group
The CDP-choline and
PEMT pathways converge
on phosphatidylcholine (PC)
synthesis in liver.
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Some of the metabolic fates for choline
Phosphatidylcholine
Sphingomyelin
Lysophosphatidylcholine
14
Phosphocholine GlycerophosphocholineAcetylcholine
Total choline = choline + Acho + PtdChol + Lyso-PtdChol + SM + GPC + PChol
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A
Artegoitia et al. (2014)15
Changes in choline status during lactation
B
C
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Choline is found in feed…
de Veth et al., 2016
16
(mg/100 g)
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…but choline is rapidly degraded in the rumen…
Sharma and Erdman, 1989
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…so flow of unprotected choline to duodenum is negligible
Sharma and Erdman, 1988
Apparent unprotected choline digestibility was 95.0 to 99.2%
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Post-ruminal delivery of choline increases choline availability in the cow
Deuchler et al, 1998
A B
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Post-ruminal delivery of choline increases arterial choline and choline-metabolites, and choline portal flux
de Veth et al., 2016
20
Data suggests increased choline utilization and storage.
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de Veth et al., 2016
21
Increased milk choline and betaine yield were observed.
Post-ruminal delivery of choline increases milk choline and choline-metabolite concentrations
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Choline feeding for fatty liver disease prevention
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Choline deficiency reduces hepatic very-low-density lipoprotein secretion and causes fatty liver in non-ruminants
A
Yao and Vance, 1990; Verkade et al., 1993; CD = choline deficient; CS = choline sufficient
B C
CD
CS
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Choline increases VLDL secretion in bovine neonatal hepatocytes
Chandler and White, 2017
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Fatty liver develops in cows with limited hepatic phosphatidylcholine (PC)
McFadden Lab (Unpublished)
25
Phosphatidylcholine
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Rumen-protected choline feeding decreases liver TAG accumulation in feed-restricted Holstein dairy cows
Zenobi et al., 2018
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Rumen-protected choline feeding increases lipoprotein TAG and phospholipids in feed-restricted Holstein dairy cows
Myers et al., 2019 (ADSA Abstract); Intake of RPC is defined as choline ion.
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LOW HIGH
Rumen-protected choline feeding increases PC within lipoprotein TAG in feed-restricted Holstein dairy cows
RPC RPC
LiverTAG-rich
lipoprotein
A
B C
Myers et al., 2019 (ADSA Abstract); ReaShure
28
Concentrations of PC
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29Zhou et al., 2018; modified figure
Black circles represent choline treatment.
Choline increases expression of genes involved phosphatidylcholine (PC) synthesis
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Erdman and Sharma, 1991
0 to 51 g/d of choline chloride/d
Effects of dietary rumen-protected choline supplementation on milk production in dairy cows
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A B
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➢ Hartwell et al., 2000 ▪ 0, 6, 12 g/d choline; -28 to 120 d
▪ Feeding RPC increased milk yield by 5.7 lb/d when cows were fed 4.0% RUP
▪ Liver triglycerides were decreased by feeding RPC to high BCS cows
➢ Piepenbrink and Overton, 2003 ▪ 0, 11.25, 18.75 g/d choline chloride; -21 to 63 d
▪ Decreased palmitate esterification in liver
▪ Increased liver glycogen
➢ Pinotti et al., 2003 ▪ 20 g/d choline chloride; -14 to 30 d
▪ RPC increased milk choline and milk yield by 6.4 lb/d (increased FCM; no change in fat %)
▪ RPC decreased NEFA on day of calving; RPC increased circulating vitamin E
Beneficial effects of dietary rumen-protected choline feeding
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➢ Zahra et al., 2006▪ 0 or 14 g/d choline chloride; -21 to 28 d
▪ RPC increased milk yield by 2.6 lbs/d; gains in cows with BCS ≥ 4.0
▪ Effects on blood NEFA and BHBA along with liver composition were not significant
➢ Elek et al., 2008, 2012▪ 0, vs. 25 with 50 g/d choline pre and postpartum; -21 to 60 d
▪ RPC increased milk yield 4.4 kg/d
▪ Increased milk choline content and yield
▪ Decreased liver triglyceride and circulating BHBA concentrations
➢ Zom et al., 2011; Goselink et al., 2013▪ 0 or 14.4 g/d choline chloride; -21 to 42 d
▪ RPC increased milk protein yield
▪ RPC decreased liver TAG but did not affect blood NEFA or BHBA
▪ RPC increased expression of genes related to processing of fatty acids and VLDL assembly
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Beneficial effects of dietary rumen-protected choline feeding
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➢ Zhou et al., 2016▪ 0 or 17.3 g/d choline chloride; -21 to 30 d; diets were low or high in metabolizable Met▪ No effect of choline feeding on milk production.▪ RPC increased blood glucose concentrations. No change for NEFA or BHBA, or liver TAG.
➢ Zenobi et al., 2018a, 2018b▪ 0 to 25 g/d choline ion; late gestating cows▪ Ad libitum fed or feed-restricted (31% of estimated requirements)▪ No changes in plasma NEFA, BHBA, glucose, insulin, and TAG▪ Increased liver glycogen concentrations▪ Linear decreases in liver TAG concentrations
▪ 0 or 17.3 g/d choline ion; -47 to 21 d▪ Fed in excess or at maintenance during prepartum▪ No change in BCS or BCS loss▪ Reduce prevalence of subclinical hypocalcemia▪ Increased milk yield; no change in DMI, plasma NEFA or liver TAG
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Beneficial effects of dietary rumen-protected choline feeding
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Sales et al., 2010
Meta-analysis of RPC feeding: Sales et al., 2010
A B
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Arshad et al., 2020
Meta-analysis of RPC feeding: Arshad et al., 2020
A B
C D
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…an “observed increased in DMI of
0.5 kg/d would likely support at least
1.1 kg of ECM, or 50% of the
observed response with supplemental
choline ion in the present study.”
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Arshad et al., 2020
Meta-analysis of RPC feeding: Arshad et al., 2020
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Increases in body weight
and body condition with
choline feeding may
contribute to reduced
hepatic fatty acid uptake
and fatty liver disease
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Arshad et al., 2020
RPC feeding increase milk fat and protein yield
37
B
+0.15 lbs of fat/d at 12.9 g choline ion/d +0.11 lbs of protein/d at 12.9 g choline ion/d
A
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A B
Arshad et al., 2020
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+3.5 lbs of milk/d at 12.9 g choline ion/d +3.8 lbs of ECM/d at 12.9 g choline ion/d
RPC feeding increase milk and ECM yields
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Santos and Lima, 2009; 0 to 15 g/d of RPC
RPC feeding has been shown to reduce disease
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A B
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Take home messages
➢ Choline has many functions including VLDL synthesis
➢ Unprotected dietary choline is subject to extensive rumen degradation
➢ Rumen-protected choline feeding…
▪ Increases plasma and milk choline and/or choline metabolite status in cows
▪ Improves liver health
▪ Increases milk/ECM production and DMI (likely dependent on improved health)
• Increased intake does not explain all gains in milk yield
▪ Decreases postpartum disease (likely a role for improved immune function)
➢ Feeding 12.5 to 20 g of rumen-protected choline ion is best throughout the transition period; especially in lower protein diets
40