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Metabolomics: Can it advance detection of metabolic disease?

Joseph W. McFadden Published on 17 October 2014

Cows on a dairy

Dairy cows transitioning from gestation to lactation are challenged with an increased energy requirement; however, energy intake is insufficient to meet this metabolic demand.

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Therefore, transition dairy cattle will experience a period of negative energy balance which promotes the release of non-esterified fatty acids (NEFA) from adipose tissue.

Sustained elevation of blood NEFA can promote excessive fat accumulation and ketone synthesis in the liver. As a consequence, transition dairy cows experiencing metabolic stress will develop fatty liver and ketosis.

Furthermore, cows with more severe negative energy balance are at greater risk for lower milk production throughout lactation, prolonged calving-to-conception interval and an increased likelihood of culling, all of which are major detriments to dairy farm profitability.

Overconditioned dairy cows exhibit a greater loss of bodyweight during the gestation to lactation transition than lean cows. The enhanced weight loss in overconditioned cows is associated with accelerated lipolysis in adipose tissue resulting in a greater elevation of circulating NEFA.

In association with elevated NEFA, overconditioned dairy cows are more prone to developing fatty liver, ketosis, systemic oxidative stress, inflammation and immunosuppression.

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Management of transition cow nutrition is critical to achieve optimum early lactation performance. Multiple approaches are recommended to improve energy balance during the transition.

Strategies include drenching with glucogenic precursors (e.g., propylene glycol) to lower plasma NEFA levels, managing cows to achieve a body condition score (BCS) of 3.25 at dry-off while maintaining this score during the dry period, feeding a low-energy diet during the far-off period while increasing the energy density of the ration a few weeks before expected calving to manage BCS gain and adapt the rumen for lactation, providing dietary supplements during the close-up period (e.g., niacin or yeast cultures), providing adequate bunk space to ensure immediate access to newly delivered feed, maximizing cow comfort and avoiding environmental stress.

Collectively, these practices can decrease the severity of appetite suppression typically observed in transition cows and serve as means to improve energy balance, health and performance.

Diagnostic evaluation of dairy cow health is a means to assess the efficacy of a transition cow program. Currently, NEFA and beta-hydroxybutyrate (BHBA) are the most commonly profiled biomarkers during the transition period. Concentrations of circulating NEFA can only be determined off-farm, in laboratories; however, urine and milk ketone levels can be rapidly measured on-farm with commercial cowside tests.

Research from Cornell University is aimed at developing critical thresholds for NEFA and BHBA that can be monitored to decrease disease risk on a herd level. Other biomarkers for stress and inflammation, characteristic for the transition period, include circulating cortisol and haptoglobin, respectively.

Despite these advancements in diagnostic screening of transition cow health, these biomarkers are limited, as are the methods to identify transition cows at greater risk for impaired health. The introduction of a contemporary, analytical approach referred to as mass spectrometry-based metabolomics has the potential to accelerate the discovery of novel biomarkers associated with disease progression in transition dairy cows.

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Mass spectrometry-based metabolomics originated in the late 1990s and is currently a mainstream approach to biomarker discovery in human biomedicine. Metabolomics methodologies have been successfully employed to expand our understanding of the mechanisms mediating Type 2 diabetes, cancer and Alzheimer’s disease.

This approach is revolutionary because it attempts to comprehensively profile hundreds of metabolites present in various biological samples including blood and urine, producing a metabolic fingerprint that can be monitored.

Once samples have been collected and processed using systematic scientific workflows, researchers employ in-depth data analysis to identify relationships between single metabolites or clusters and disease progression. Due to greater metabolite identification, accessibility and sample throughput, as well as lower costs and ease of use, application of metabolomics in dairy science research is now possible.

At West Virginia University, the McFadden Laboratory is utilizing metabolomics to identify the mechanisms that cause metabolic disease in transition dairy cows. Ongoing research supported by the USDA Agriculture and Food Research Initiative as well as the USDA Northeast Sustainable Agriculture Research and Education program aims to profile more than 150 metabolites in lean and overconditioned transition dairy cows.

First, the lab will characterize their metabolomes by targeting molecules associated with elevated NEFA in monogastric animal models. The lab has focused their attention on a class of lipids called sphingolipids, biomarkers for metabolic disease in overweight mice and humans.

An aim is to profile sphingolipids and identify their potential to predict cows at greater risk for poor health after calving. Second, the lab will use a more comprehensive method to determine the relative concentrations of all detectable metabolites in carbohydrate, lipid and amino-acid metabolism.

Metabolite profiles derived from both approaches will be compared to dairy cow physiology during the transition period. In turn, novel biomarkers will emerge that may be used to predict whether a herd is at high or low risk for developing postpartum disease.

To develop new diagnostic approaches so transition dairy cow health can be improved, the McFadden Laboratory and West Virginia University have established a strong relationship with DoVan Farms, a 700-Holstein dairy farm in Berlin, Pennsylvania. DoVan Farms is owned and operated by the VanGilder family and operates an anaerobic digester and an impressive 132-foot-tall cement silo holding 3,000 tons of corn silage.

The farm is equipped with multiple cow weigh and biopsy stations, an individual cow feeding system for transition cow research, an activity monitoring system, milk samplers for the double-16 parallel parlor, a sample preparation laboratory and a self-propelled mini-TMR mixer for experimental TMR formulation.

Furthermore, the VanGilder family is receptive to adding to these on-farm research capabilities and developing an undergraduate internship program.

In addition to this agricultural partnership, the McFadden lab has established a regional network across Pennsylvania, Maryland and West Virginia that includes dairy producers, veterinarians, nutritionists and extension agents to test the effectiveness of newly discovered biomarkers to predict disease risk, and develop and test practical interventions aimed at improving herd health, milk production and quality, fertility and farm profitability.

It is clearly evident that prepartum concentrations of NEFA or BHBA are associated with increased risk for postpartum disease, compromised milk production and impaired fertility. Research should continue to evaluate the potential for these biomarkers to predict disease risk in transition cows.

With the dawn of metabolomics in dairy science, the discovery of new biomarkers for metabolic disease in cattle is probable. Whether these biomarkers will serve as better predictors for transition dairy cow disorders remains to be determined.

It can’t be overemphasized that a diagnostic testing routine can be a valuable tool to monitor the health of a transition cow program, and with continued research, the ability to identify at-risk herds will certainly continue to improve. PD

Photo by PD staff.

Joseph W. McFadden
Assistant Professor of Biochemistry
Division of Animal and Nutritional Sciences
West Virginia University

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