Slide 1: Choline biology in dairy cattle: Contemporary perspectives and future prospects
5/1/20 Choline biology in dairy cattle: Contemporary perspectives and future prospects Joseph W. McFadden, Ph.D. Associate Professor of Dairy Cattle Biology Northeast Agribusiness & Feed Alliance Faculty Fellow Department of Animal Science McFadden@cornell.edu Presented as a webinar for the Methyl D
Slide 2: …but this is not your average choline talk
5/1/20 …but this is not your average choline talk: What's in the research pipeline and why does it matter? Ø Topic #1: How might fatty acid nutrition optimize choline efficacy? Ø Topic #2: Should we be concerned about lower gut choline degradation and trimethylamine N-oxide? Ø Topic #3: Why should w
Slide 3: Fatty liver develops in cows with low phosphatidylcholine
5/1/20 Dietary choline and fatty liver prevention: Charles Best & Fredrick Banting 5 Hershey and Soskin, 1931; Zeisel et al., 2012 Fatty liver develops in cows with low phosphatidylcholine Phosphatidylcholine…. more than just choline 6 McFadden Lab (Unpublished); plasma 3
Slide 4: Rumen-protected choline feeding has been shown to lower liver triglyceride accumulation in fresh cows
5/1/20 Rumen-protected (RP) choline feeding has been shown to lower liver triglyceride accumulation in fresh cows Ø Hartwell et al., 2000 § 0, 6, 12 g/d choline; -28 to 120 d § Liver triglycerides were decreased by feeding RPC to high BCS cows Ø Elek et al., 2008, 2012 § 0, vs. 25 with 50 g/d cholin
Slide 5: Rumen-protected choline feeding increases VLDL-PtdChol in prepartum Holstein cows
5/1/20 Rumen-protected choline feeding increases VLDL-PtdChol prepartum Holstein dairy cows experiencing negative energy status Ø RP-choline feeding… VLDL PtdChol, Fold-change § Increased hepatic phosphatidylcholine § Increased plasma VLDL-TAG Phosphatidylcholines § Decreased liver TAG Zenobi et al.
Slide 6: Abomasal choline infusion differentially modifies hepatic PtdChol supply in cows
5/1/20 Abomasal choline infusion differentially modifies hepatic PtdChol supply in cows A -/+ abomasal choline B PtdChol-32:1 (16:0/16:1) C PtdChol-36:6 (14:0/22:6) auto-scaled intensities Transformed ≥ 2-fold difference -Choline +Choline -Choline +Choline Likely made from CDP- Likely made from chol
Slide 7: In humans, DHA + choline promotes PEMT pathway activation
5/1/20 In humans, DHA + choline promotes PEMT pathway activation in humans DHA + Choline Control Choline DHA 13 Bernhard et al., 2019 Feeding prilled palm fatty acids containing less C16:0/more C18:1 increased plasma total choline in lactating dairy cows 14 Wang et al., In Review; P-values based on
Slide 8: Conclusion #1
5/1/20 Conclusion #1 Ø Low PtdChol supply is a key feature of fatty liver in dairy cows. § Likely due to low PUFA and choline Ø Delivery of post-ruminal PUFA may support PtdChol synthesis in cows. § Should consider interactions with dietary fatty acid digestibility § Improved insulin sensitivity, an
Slide 9: Unprotected choline is degraded to trimethylamine in rumen
5/1/20 Choline is degraded to trimethylamine (by microbes), which is converted to trimethylamine N-oxide (TMAO) in liver Choline Trimethylamine TMAO 17 Cho and Caudill, 2017 Unprotected choline is degraded to trimethylamine in rumen A B Trimethylamine Choline Choline à trimethylamine Hayward and Sta
Slide 10: Feeding phosphatidylcholine increases plasma TMAO in lactating cows
5/1/20 Feeding phosphatidylcholine (i.e., lecithin) increases plasma [TMAO] in lactating cows 19 Wang et al., In Review Abomasal infusion of choline chloride increases plasma [TMAO] in lactating cows A B C 40 35 35 P-value <0.0001 P-value <0.05 30 * Choline, nmol/mL * TMAO, nmol/mL 30 25 25 20 20 15
Slide 11: TMAO accumulation is related to poor health
5/1/20 TMAO accumulation is related to poor health Ø Non-alcoholic fatty liver disease Ø Inflammation Ø Insulin resistance (type-2 diabetes) Ø Obesity Trimethylamine reported in cows Ø Oxidative stress Ø Cardiovascular disease Ø Cancer Ø CKD (Chronic kidney disease) Plasma [TMAO] has been shown to b
Slide 12: Acute intravenous TMAO infusion does not modify milk production in early lactation cows
5/1/20 Acute intravenous TMAO infusion does not modify milk production in early lactation cows 23 Replicated 4 × 4 Latin square; 8 cows; continuous i.v. infusion Acute intravenous TMAO infusion does not modify glucose tolerance in early lactation cows A B No change in basal glucose, triglyceride, or
Slide 13: Conclusion #2 / Topic #3: Lysophosphatidylcholine and Immunomodulation
5/1/20 Conclusion #2 Ø Trimethylamine N-oxide does not appear to influence energy metabolism or challenge health in early lactation cows. Ø Choline is subject to ruminal and lower-gut degradation to trimethylamine. § The influence on choline bioavailability needs to be defined. Ø Data in non-ruminan
Slide 14: Neutrophils and immunity
5/1/20 Neutrophils and immunity A Ø Neutrophils are cells of the innate immune system (first line of defense). Ø Help fight infection by ingesting microorganisms and releasing enzymes to kill invaders. B Ø Involves the production of oxygen free radicals (i.e., oxidative burst). Ø Pre-weaned calves a
Slide 15: The endotoxin response in lactating cows
5/1/20 The endotoxin response in lactating cows A B C Trt×Time: P < 0.01 29 The Baumgard Lab Endotoxin decreases circulating lysophosphatidylcholines in dairy cows A B D C 30 McFadden et al., (unpublished) 15
Slide 16: Lysophosphatidylcholine therapy prevents sepsis-induced mortality
5/1/20 31 Lysophosphatidylcholine therapy prevents sepsis- induced mortality A B LPC activates innate and adaptive immunity. 32 Yan et al., 2004 16
Slide 17: Saturated LPC enhances oxidative burst in neutrophils isolated from pre-weaned calves
5/1/20 Saturated LPC enhances oxidative burst in neutrophils isolated from pre-weaned calves C16:0-LPC C18:0-LPC A B PMA PMA PMA = phorbol myristate acetate (promotes oxidative burst); pilot data; 33 ROS production = chemiluminescence Rumen-protected choline feeding increases circulating LPC RP-chol
Slide 18: Conclusion #3
5/1/20 Conclusion #3 Ø Immunosuppression and endotoxemia are characterized by low circulating lysophosphatidylcholine concentrations in dairy cows. Ø In vitro data suggest that saturated LPC activate neutrophils. Ø Rumen-protected choline feeding increases circulating LPC. § Future research is likel
Slide 19: Questions?
5/1/20 The lab Collaborators Ø Dr. Eduardo Rico (Post-doc) Ø Dr. Charles Staples Ø Philip Wang (visiting postdoc) Ø Dr. Lance Baumgard Ø Amanda Davis (PhD student; NSF Fellow) Ø Dr. Norman Haughey Ø Ananda Fontoura (PhD student; FFAR Fellow) Ø Brianna Tate (PhD student) Ø William Myers (PhD student)