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 [email protected] 1 Presented 1.28.20
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
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?
2
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
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
A B
Drackley, 1999; Aschenbach et al., 2010
A healthy liver benefits the transition cow
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
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
Fatty liver is associated with the development of other postpartum disorders
Bobe et al., 2004
Fatty liver impairs fertility in dairy cows
Bobe et al., 2004
The origins of choline:Theodore Gobley, Adolph Strecker and Oscar Liebreich
10Zeisel et al., 2012
The origins of choline: Charles Best and Fredrick Banting
11Hershey and Soskin, 1931; Zeisel et al., 2012
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
12
Choline metabolism
1313
A methyl group
The CDP-choline and
PEMT pathways converge
on phosphatidylcholine (PC)
synthesis in liver.
Some of the metabolic fates for choline
Phosphatidylcholine
Sphingomyelin
Lysophosphatidylcholine
14
Phosphocholine GlycerophosphocholineAcetylcholine
Total choline = choline + Acho + PtdChol + Lyso-PtdChol + SM + GPC + PChol
A
Artegoitia et al. (2014)15
Changes in choline status during lactation
B
C
Choline is found in feed…
de Veth et al., 2016
16
(mg/100 g)
…but choline is rapidly degraded in the rumen…
Sharma and Erdman, 1989
17
…so flow of unprotected choline to duodenum is negligible
Sharma and Erdman, 1988
Apparent unprotected choline digestibility was 95.0 to 99.2%
18
Post-ruminal delivery of choline increases choline availability in the cow
Deuchler et al, 1998
A B
19
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.
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
22
Choline feeding for fatty liver disease prevention
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
23
Choline increases VLDL secretion in bovine neonatal hepatocytes
Chandler and White, 2017
24
Fatty liver develops in cows with limited hepatic phosphatidylcholine (PC)
McFadden Lab (Unpublished)
25
Phosphatidylcholine
Rumen-protected choline feeding decreases liver TAG accumulation in feed-restricted Holstein dairy cows
Zenobi et al., 2018
26
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.
27
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
29Zhou et al., 2018; modified figure
Black circles represent choline treatment.
Choline increases expression of genes involved phosphatidylcholine (PC) synthesis
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
➢ 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
31
➢ 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
➢ 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
33
Beneficial effects of dietary rumen-protected choline feeding
Sales et al., 2010
Meta-analysis of RPC feeding: Sales et al., 2010
A B
34
Arshad et al., 2020
Meta-analysis of RPC feeding: Arshad et al., 2020
A B
C D
35
…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.”
Arshad et al., 2020
Meta-analysis of RPC feeding: Arshad et al., 2020
36
Increases in body weight
and body condition with
choline feeding may
contribute to reduced
hepatic fatty acid uptake
and fatty liver disease
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
A B
Arshad et al., 2020
38
+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
Santos and Lima, 2009; 0 to 15 g/d of RPC
RPC feeding has been shown to reduce disease
39
A B
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
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