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

McFadden@cornell.edu

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

30

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

32

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

40