ROLE OF NEFA AND BHBA AS A PREDICTIVE MARKER IN PREDICTING METABOLIC DISEASES & PERFORMANCE DURING TRANSITION PERIOD
Advances in genetic techniques has resulted in improvement in dairy cows markedly increasing milk yield over the last three decades. But this increased milk production is often associated with poor reproductive performance and other metabolic disorders. Transition period as described by Grummer, (1995) is the most vulnerable and critical period experienced by cow that extends from three weeks prepartum to three weeks postpartum. During this period cow undergoes major physiological, nutritional, immunological, endocrine and metabolic changes that are necessary for the cow to shift from gestational non-lactating stage to parturition and lactogenesis. Hayirli et al. (2002) reported one-third decrease in feed intake experienced by the cow during last three weeks prior to calving and significant reduction in final week before parturition. This is mainly due to less capacity for rumen to expand because of increased size of foetus and high concentrations on estrogens levels. After parturition there is increase in demand for nutrient and energy for lactation but the inability of the cow to cope with the increasing energy demands due to decreased DMI results in negative energy balance. To meet the energy requirements depletion of body fat stores occurs. These processes are accompanied by elevated blood concentrations of non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) and decreased levels of calcium and phosphorous leading to metabolic disorders. Production diseases are the result of cow’s inability to cope with the high metabolic demands of lactation. The term ‘production disease’ encompassed metabolic disorders like ketosis, hypocalcaemia (milk fever) and hypomagnesaemia (grass tetany) but the term has been broadened to include associated clinical diseases like retained placenta, metritis, endometritis, and displaced abomasum (Mulligan and Doherty, 2008). These production diseases are associated with severe economic losses in terms of heavy reduction in milk yield and impaired reproductive performance.
NEFA and BHBA Level as a Predictive Marker of Transition Cow Health and Performance:
NEB is an important characteristic of transition cow particularly in high yielding animals, due to the integrative outcome of reduced intake and higher demand for maintenance and production. NEFA and BHBA are important energy metabolites that are traditionally used as indicators of NEB during transition period An elevation of NEFA and BHBA during the transition period is the metabolic hallmark of the transition from pregnancy to lactation particularly in high-yielding dairy cows. However, an excessive elevation of these metabolites is often associated with poor productive and reproductive performance. The release of NEFA into the blood provides energy to tissues; however, the bovine liver has a limited capacity to metabolize NEFA into triglycerides (TAG). When the limit is reached, the TAG accumulates in the liver, and acetyl CoA (resulting from oxidation of fatty acids) is not utilized in the tricarboxylic acid cycle which is converted into ketone bodies such as acetone, acetoacetate, and BHBA which may appear in the blood, milk, and urine . Excessive accumulation of TAG in the liver impairs its normal function . The synthesis and accumulation of TAG in the liver are related to the concentration of NEFA in the blood; therefore, cows with lipolysis are at high risk to develop fatty liver syndrome . In addition, development of fatty liver has been found to impair the gluconeogenic activity of the liver, which lowers blood glucose and decreases insulin secretion. This, in turn, would support greater lipid mobilization and increased rate of fatty acid uptake by the liver and increased ketogenesis . An imbalance of energy requirement and nutrients intake often leads to various metabolic disorders such as fatty liver, ketosis (clinical or subclinical), ruminal acidosis (subacute or acute), milk fever (subclinical or clinical), and disturbed immune function (retained placenta, Met, and mastitis). The collective effects of all these challenges are leads to reduced fertility and milk production in short and long term. Due to direct and indirect relationship of metabolites with productive and reproductive performance, these molecules have been extensively used for assessment of herd or individual animal health performance. However, the only concerns with these molecules are different threshold level practised across the countries and studies (Table-1) [14,39,44-56]. For instance, threshold concentration of NEFA and BHBA from ≥0.3 to 0.5 mEq/L and ≥0.6 to 0.8 mmol/L, respectively, during prepartum period and from ≥0.7 to 1.0 mEq/L and 1.0 to 1.4 mmol/L, respectively, during postpartum period were used to evaluate the individual cow association with negative outcome in various studies . Although management systems, parity, yield of animals, period of sampling, and targeted disease outcome were the possible explanations for these variations, underlying physiological mechanisms are poorly understood. To establish the cutoff or threshold values of NEFA and BHBA, Ospina et al. [48,49,58] conducted a large-scale study in 100 herds (1440 prepartum and 1318 postpartum cows; 35% primiparous and 65% multiparous cows) through sampling of 2758 transition cows (14 to 2 days before calving and 3-14 days after calving) and established critical threshold values for prepartum NEFA and postpartum NEFA and BHBA to predict the disease (displaced abomasum [DA], clinical ketosis [CK], Met, and retained fetal membranes (RFM), within 30 days in milk (DIM), and impact on fertility within 70 days after voluntary waiting period [VWP]) risk ratio. They established threshold level for prepartum NEFA concentration as 0.3 mEq/L and postpartum NEFA concentration as 0.6 mEq/L and 10 mg/dL as postpartum BHBA threshold level. Animals with NEFA and BHBA concentrations above these threshold levels during prepartum and postpartum period had 2 and 4 times higher disease incidence, respectively. They also found that the animals with above critical prepartum NEFA level were 20% less likely become pregnant after 70 days of VWP, while cows with above critical levels of postpartum NEFA and or BHBA were 13-16% less likely to become pregnant and multiparous cows suffered more than primiparous cows. Overall, herd with >15% of transition cows above the critical value . It may be inferred from the above-cited findings that measurement of energy indicators is a useful tool for herd health evaluation and improved transition cow management.
Milk fever (hypocalcaemia)
Incidence rates of clinical hypocalcaemia vary between 3.5 and 7% (De Garis and Lean, 2008). After parturition, there is increased calcium demand for lactation and colostrum production and to meet this demand calcium mobilisation from bones occurs. Milk fever occurs if the calcium homeostasis mechanism which normally maintain blood calcium levels between 9 and 10 mg/dl fails to keep up with the lactational demands resulting in blood calcium levels to fall below 5mg/dl (NRC, 2001). This hypocalcaemia impairs muscle and nerve function to such a degree that the animal is unable to rise. Hypocalcaemia is associated with many other disorders like dystocia, retained placenta, endometritis, infertility, uterine prolapse, mastitis, displaced abomasum, and ketosis (Houe et al. 2001). Intravenous calcium treatments (calcium borogluconate) are used to keep the cow with milk fever alive long enough for calcium homeostatic mechanisms to adapt.
Grass tetany (hypomagnesaemia)
Grass tetany occurs due to low level of magnesium in the blood and is often associated with early lactation as 0.15g magnesium is removed from the blood per litre of milk production. Animals grazing on lush green pastures or potassium fertilized pastures are more prone to grass tetany as potassium interfere with the absorption of magnesium thus leading to deficient levels of magnesium in blood.
Fatty liver and ketosis
During early lactation dietary nutrient supply is unable to meet the nutrient and energy demand of lactation and decreased DMI associated with high estrogen levels and less space in rumen to expand due to foetus leads to negative energy balance (NEB). To cope with the negative energy balance mobilisation of non-esterified fatty acids (NEFA) from adipose tissue occurs. The extent of lipid mobilisation depends on the period of negative energy balance experienced by the animal. Uptake of NEFA by liver is proportional to NEFA concentrations in blood (Bell, 1979). Higher rates of lipid mobilisation led to higher intake of NEFA by liver. Non-esterified fatty acids (NEFA) taken up by liver can either be esterified or oxidised. Esterification of NEFA results in the formation of triglycerides which are either exported as very low-density lipoprotein (VLDL) or stored in liver. The rate at which the export of triglyceride occurs is very slow as compared to other species (Kleppe et al., 1988; Pullen et al., 1990). Thus, leading to accumulation of triglycerides (TG) in liver resulting in fatty liver.
Oxidation of Non-esterified fatty acids (NEFA) lead to either formation of carbon dioxide and ATP or ketone bodies like β-hydroxybutyrate (BHBA). Complete oxidation of NEFA in liver leads to production of energy and carbon dioxide where as incomplete oxidation leads to formation of ketone bodies leading to ketosis. Low levels of insulin enhance fatty acid oxidation by decreasing hepatocyte malonyl CoAwhich in an inhibitor of Carnitine plamitoyltranferase-1 which is responsible for translocation of fatty acid from cytoplasm to mitochondria for oxidation.
Prediction of clinical diseases through NEFA and BHBA levels
Ospina et al. (2010) reported that serum levels of NEFA and BHBA during transition period can be used to predict the occurrence of periparturient diseases like displaced abomasum, ketosis, metritis and retained placenta within 30 days in milk. Ospina et al. (2010) calculated threshold values for both NEFA and BHBA and values higher than the threshold values were associated with the incidence of periparturient diseases or production diseases. Ospina et al. (2010) reported that NEFA concentrations of ≥ 0.29 mEq/L prepartum and ≥ 0.57 mEq/L postpartum were associated with the risk of developing displaced abomasum, metritis, or retained placenta during the first 30 d in milk and BHBA concentrations of ≥1.0 mmol/L from day 3 to 14 postpartum were associated with increased risk of clinical ketosis as well as metritis. Transition period is the most vulnerable period that is associated with peak incidences of metabolic diseases like ketosis, milk fever, fatty liver and results in detrimental effect on cow’s performance. By evaluating the serum levels of non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) in late prepartum and early postpartum period, incidences or occurrence of metabolic diseases can be predicted as well as prevented by timely nutritional intervention which leads to better health and performance of the cow.
NEB is an important characteristic of transition cows, and it is a normal adaptive mechanism in high yielding dairy animals. Although changes in the energy and nutrient intake along with hormonal environment toward parturition were thought as major determinants of NEB, recent evidence indicate that hepatic inflammatory responses during periparturient period are an important driving force for fat mobilization. Physiological adaptation to metabolic processes in periparturient cow starts well in advance of parturition, and it is mainly regulated by cytokines, acutephase proteins, and energy metabolites. Despite a clear understanding of cause and consequence of many periparturient complications, cellular and molecular studies to associate these events are less. At present, several association studies between energy balance during transition period and subsequent postpartum performance are available; however, further studies are required, particularly in moderate yielding Indian dairy cattle, for effective postpartum management.
Compiled & Shared by- Team, LITD (Livestock Institute of Training & Development)
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