Fatty acids, lipids considered in novel approach to fatty liver disease

Joe McFadden, assistant professor in the department of animal science at Cornell University, presented on research being done to address fatty liver disease in during his talk at the Cornell Nutrition Conference for Feed Manufacturers earlier this autumn.

Fatty liver disease is quite common in dairy cows and has been a focus of research for some time, he told FeedNavigator. “What we’re doing is using a different angle.”​

The disease continues to be of interest because it is linked to poorer health, a reduction in fertility and reduced lactation performance, he said in his presentation paper. Cows with the disease also are at risk of other diseases including mastitis.

McFadden’s research has been taking some cues from work done on humans or in medical research for humans and it mapped the bovine glycerophospholipidome, he told us.

“This is the first time trying to manage that data, and then we need to know where to look,” ​he said. “So, we rely on the biomedical research, which has been using that technology for over a decade now and we’re just starting to use it, so we know where to look based on that.”​

A recent proof-of-principal project saw a group of cows given one of five emulsions for a six-day period to track the influence of the different supplements regarding hepatic and circulating phosphatidylcholine (​PC) concentration, he said in his presentation. More research is needed, but the current data suggest that supplemental choline and DHA may activate the cytidine diphosphate (CDP)-choline pathway and the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, respectively.

“Rumen-protected choline and DHA co-supplementation may optimize hepatic PC synthesis – choline is activating one … DHA is activating the other pathway,” ​he said. “What happens when you put the two together –​ that’s actively being explored.”​

Combining rumen-protected DHA and choline may be a way to address the root causes of the disease, said McFadden. “It’s best to feed a nutrient and know that you’re targeting the root mechanism of the disease and that’s what we’re trying to do – characterize disease mechanisms and then use nutrition prevent those mechanisms and fatty liver disease from developing,”​ he added.

Additionally, fatty acid nutrition needs attention, he said. “Liver health can potentially be influenced by specific types of fatty acids and we need to start to research this area because it’s something we’ve ignored. We’ve focused on methyl donors nutrition because of their ability to target phosphatidylcholine synthesis but it appears that unique fatty acids may promote or prevent fatty liver from developing​ – we have to broaden our vision here.”​

Addressing fatty liver disease​

The research is focused on finding a way to address the disease through nutrition, said McFadden. Although there are rumen-protected methyl donor products designed to increase triglyceride or fat export from the liver, their efficacy may vary.

"We believe that the fatty acid feeding regimen needs to be considered when supplementing with methyl donors because certain types of fatty acids may enhance or even prevent the intended action of methyl donors," ​he said. "This is a question worth asking and will help farmers gain maximum benefit from feeding these types of supplements."​

The line of questioning explores what role fatty acids could play in preventing or exacerbating fatty liver disease, he said. “Although we have focused on the role of methyl donors during phosphatidylcholine synthesis, we have ignored the role of fatty acids which are key for their synthesis​,” ​he added.

Fatty acids and methyl donors are among the components needed to generate phosphatidylcholine, he said.

“There’s a general agreement that limited phosphatidylcholine synthesis is a contributing factor to fatty liver disease,”​ McFadden said. “We’ve generalized the role of phosphatidylcholine synthesis but we now know that their synthesis is complex. Different substrates (methyl donors and fatty acids) influence which pathway is activated. We need to learn how to optimize the activation of both pathways so we maximize phosphatidylcholine synthesis and triglyceride secretion from the liver.”​​

In the proof-of-principal study, the compounds trialed were palmitic acid (PA), palmitic acid and choline chloride, palmitic acid and L-serine, behenic acid and a mixed omega-3 oil that included DHA and EPA, he said in his presentation paper. None of the supplements altered circulating glucose or total fatty acid concentration, although cholesterol and circulating triacylglycerol (TAG) concentrations were highest with palmitic acid and lowest with the omega-3.

In the study, high DHA supplementation into the abomasum increased the synthesis of phosphatidylcholines containing long-chain polyunsaturated fatty acids when compared to cows receiving the PA infusion, he said.

The group also saw the DHA infusion reduce dry matter intake and milk yield. It is now testing feeding smaller amounts of rumen-protected DHA, which is not anticipated to alter intake or milk production, he said, adding, "We also still expect to observe gains in phosphatidylcholine synthesis at a lower feeding level."​

“Current evidence suggests that choline and DHA supplementation predominately activate the CDP-choline and PEMT pathways respectively,”​ he added.

Fatty acid nutrition has changed in recent years, McFadden told us. For almost 20 years, one focus has been on fatty acid nutrition was as a way to alter milk fat production, but an expanded understanding of the topic has shown that fatty acid feeding influences metabolic health.

“Now we know that there are signaling molecules made by certain types of fatty acids that influence health and metabolism in other ways outside of the mammary gland and that’s opening up a lot of doors for new research,” ​​he said. “Because the dairy cow lipidome has thousands of complex lipids with unique structural and functional attributes – we’re just getting started."​​

Looking forward​

The proof-of-principal trial started used a basic science approach to find the relevant portion of a cow’s lipidome, said McFadden. “That’s what this project was – we discovered where to look in the lipidome – that DHA and choline co-supplementation might have added benefit,”​ he added.

“By this time next year, we’ll have a good idea whether co-supplementation is effective,”​ he said. There are several trials set for 2019, including looking at DHA and choline along with efforts to find a new way to run ex vivo models, he added. 

Another future move forward is to develop a potential product based on the information generated, he said. “We’re working with industry to develop such a rumen-protected DHA supplement to optimize transition cow nutrition and health​,”​ he added.

“There are some products that are out there, but, in my opinion, they’re underdeveloped,”​ he said. “In the future, it is likely that we will see more rumen-protected DHA supplements or fatty acid feeding recommendations that optimize the benefits of feeding methyl donors such as choline or methionine."​​