scholarly journals A Multi-Platform Metabolomics Approach Identifies Urinary Metabolite Signatures That Differentiate Ketotic From Healthy Dairy Cows

2021 ◽  
Vol 8 ◽  
Author(s):  
Guanshi Zhang ◽  
Rupasri Mandal ◽  
David S. Wishart ◽  
Burim N. Ametaj

Ketosis and subclinical ketosis are widespread among dairy cows especially after calving. Etiopathology of ketosis has been related to negative energy balance. The objective of this study was to investigate metabolite fingerprints in the urine of pre-ketotic, ketotic, and post-ketotic cows to identify potential metabolite alterations that can be used in the future to identify susceptible cows for ketosis and metabolic pathways involved in the development of disease. In this study, NMR, DI/LC-MS/MS, and GC-MS-based metabolomics were used to analyze urine samples from 6 cows diagnosed with ketosis and 20 healthy control (CON) cows at −8 and −4 weeks prepartum, the week (+1 to +3) of ketosis diagnosis, and at +4 and +8 weeks after parturition. Univariate and multivariate analyses were used to screen metabolite panels that can identify cows at their pre-ketotic stage. A total of 54, 42, 48, 16, and 31 differential metabolites between the ketotic and CON cows were identified at −8 and −4 weeks prepartum, ketosis week, and at +4, and +8 weeks postpartum, respectively. Variable importance in projection (VIP) plots ranked the most significant differential metabolites, which differentiated ketotic cows from the CON ones. Additionally, several metabolic pathways that are related to ketosis were identified. Moreover, two promising metabolite panels were identified which clearly separated ketotic from CON cows with excellent level of sensitivity and specificity. Overall, multiple urinary metabolite alterations were identified in pre-ketotic, ketotic, and post-ketotic cows. The metabolite panels identified need to be validated in the future in a larger cohort of animals.

2019 ◽  
Vol 74 (10) ◽  
pp. 6133-2019
Author(s):  
YUANYUAN CHEN ◽  
ZHIHAO DONG ◽  
RUIRUI LI ◽  
CHUANG XU

Negative energy balance (NEB) is a common pathological cause of ketosis. As the major organs of lipid metabolism, the liver and fat tissue take part in regulating lipid oxidative capacity and energy demands, which is also a key metabolic pathway that regulates NEB development during the perinatal period. Fibroblast Growth Factor 21 (FGF21) is a novel metabolic regulator involved in the control of fatty acid oxidation and lipid metabolism during a prolonged negative energy balance. Our study determined a correlation between serum FGF21 and β-hydroxybutyric acid (BHBA) levels in dairy cows with ketosis. We used sixty cows with low milk yield, abnormal glucose metabolism, and ketosis. Serum FGF21 and BHBA levels were measured using commercial kits. Serum FGF21 increased with increasing BHBA levels up to 1.6 mmol/L. At BHBA levels > 1.6 mmol/L, FGF21 decreased. Serum FGF21 levels were positively associated with BHBA levels, particularly in dairy cows with subclinical ketosis (r = 0.647, P < 0.01). At BHBA levels between 1.2 mmol/L and 1.6 mmol/L, FGF21 was more closely correlated with BHBA than with other metabolic parameters. At BHBA levels > 1.6 mmol/L, the association between FGF21 and BHBA was not significant. In conclusion, our results show that FGF21 was closely related with SK in cows. FGF21 may be a promising regulator in the prevention of subclinical ketosis.


2011 ◽  
Vol 31 (suppl 1) ◽  
pp. 11-17 ◽  
Author(s):  
Alejandra M.B García ◽  
Felipe C Cardoso ◽  
Rómulo Campos ◽  
Diego X Thedy ◽  
Félix H.D González

In early lactation dairy cattle suffer metabolic alterations caused by negative energy balance, which predisposes to fatty liver and ketosis. The aim of this study was to evaluate the metabolic condition of high yielding dairy cows subjected to three treatments for preventing severe lipomobilization and ketosis in early lactation. Fifty four multiparous Holstein cows yielding >30 L/day were divided into four groups: control (CN= no treatment), glucose precursor (PG= propylene-glycol), hepatic protector (Mp= Mercepton®), and energy supplement with salts of linolenic and linoleic faty acids (Mg-E= Megalac-E®). Treatments were administrated randomly at moment of calving until 8 weeks postpartum. Blood samples were collected on days 1, 7, 14, 21, 28, 35, 42 and 49 postpartum. Body condition score (BCS) was evaluated at the same periods and milk yield was recorded at 2nd, 4th, 5th, 6th, 7th, and 8th weeks of lactation. Concentrations of non-esterified fatty acids (NEFA), albumin, AST, ß-hydroxybutyrate (BHBA), cholesterol, glucose, total protein, urea and triglycerides were analyzed in blood samples. Cut-off points for subclinical ketosis were defined when BHBA >1.4 mmol/L and NEFA >0.7 mmol/L. General occurrence of subclinical ketosis was 24% during the period. An ascendant curve of cholesterol and glucose was observed from the 1st to the 8th week of lactation, while any tendency was observed with BHBA and NEFA, although differences among treatments were detected (p<0.05). BCS decreased from a mean of 3.85 at 1st week to 2.53 at 8th week of lactation (p=0.001). Milk yield was higher in the Mg-E group compared with the other treatment groups (p<0.05) Compared with the CN group, the treatments with Mp and PG did not show significant differences in blood biochemistry and milk yield. Cows receiving PG and Mg-E showed higher values of BHBA and NEFA (P<0.05), indicating accentuated lipomobilization. Supplementation with Mg-E also resulted in significant higher concentrations of cholesterol, BHBA, urea, AST and lower values of glycemia. This performance may be explained by the highest milk yield observed with this treatment. Treatments with PG and Mp did not improve milk yield, compared with control cows, but did not show metabolic evidence of ketosis, fat mobilization or fatty liver. These results suggest that treatment with Mg-E improves milk production but induces a higher negative energy balance leading to moderated lipomobilization and ketone bodies production, increasing the risk of fatty liver.


Proceedings ◽  
2020 ◽  
Vol 73 (1) ◽  
pp. 9
Author(s):  
Deise Aline Knob ◽  
André Thaler Neto ◽  
Helen Schweizer ◽  
Anna Weigand ◽  
Roberto Kappes ◽  
...  

Depending on the breed or crossbreed line, cows have to cope with a more or less severe negative energy balance during the period of high milk yields in early lactation, which can be detected by beta-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFAs) in blood. Preventing cows from undergoing a severe negative energy balance by breeding and/or feeding measures is likely to be supported by the public and may help to improve the sustainability of milk production. The aim was to compare BHBA and NEFA concentrations in the blood of Holstein and Simmental cows and their crosses during the prepartum period until the end of lactation. In total, 164 cows formed five genetic groups according to their theoretic proportion of Holstein and Simmental genes as follows: Holstein (100% Holstein; n = 9), R1-Hol (51–99% Holstein; n = 30), F1 crossbreds (50% Holstein, 50% Simmental; n = 17), R1-Sim (1–49% Holstein; n = 81) and Simmental (100% Simmental; n = 27). NEFA and BHBA were evaluated once a week between April 2018 and August 2019. A mixed model analysis with fixed effects breed, week (relative to calving), the interaction of breed and week, parity, calving year, calving season, milking season, and the repeated measure effect on cows was used. Holstein cows had higher NEFAs (0.196 ± 0.013 mmol/L), and Simmental cows had the lowest NEFA concentrations (0.147 ± 0.008 mmol/L, p = 0.03). R1-Sim, F1 and R1-Hol cows had intermediate values (0.166 ± 0.005, 0.165 ± 0.010, 0.162 ± 0.008 mmol/L; respectively). The highest NEFA value was found in the first week after calving (0.49 ± 0.013 mmol/L). BHBA did not differ among genetic groups (p = 0.1007). There was, however, an interaction between the genetic group and week (p = 0.03). While Simmental, R1-Sim and F1 cows had the highest BHBA value, the second week after calving (0.92 ± 0.07 and 1.05 ± 0.04, and 1.10 ± 0.10 mmol/L, respectively), R1-Hol and Holstein cows showed the BHBA peak at the fourth week after calving (1.16 ± 0.07 and 1.36 ± 0.12 mmol/L, respectively). Unexpectedly, Holstein cows had a high BHBA peak again at week 34 after calving (1.68 ± 0.21 mmol/L). The genetic composition of the cows affects NEFA and BHBA. Simmental and R1-Sim cows mobilize fewer body reserves after calving. Therefore, dairy cows with higher degrees of Simmental origin might be more sustainable in comparison with Holstein genetics in the present study.


Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1674
Author(s):  
Ilona Strączek ◽  
Krzysztof Młynek ◽  
Agata Danielewicz

A significant factor in improving the performance of dairy cows is their physiological ability to correct a negative energy balance (NEB). This study, using Simmental (SIM) and Holstein-Friesian (HF) cows, aimed to assess changes in NEB (non-esterified fatty acid; body condition score; and C16:0, C18:0, and C18:1) and its effect on the metabolic efficiency of the liver (β-hydroxybutyrate and urea). The effects of NEB on daily yield, production at peak lactation and its duration, and changes in selected milk components were assessed during complete lactation. Up to peak lactation, the loss of the body condition score was similar in both breeds. Subsequently, SIM cows more efficiently restored their BCS. HF cows reached peak lactation faster and with a higher milk yield, but they were less able to correct NEB. During lactation, their non-esterified fatty acid, β-hydroxybutyrate, C16:0, C18:0, C18:1, and urea levels were persistently higher, which may indicate less efficient liver function during NEB. The dynamics of NEB were linked to levels of leptin, which has anorectic effects. Its content was usually higher in HF cows and during intensive lactogenesis. An effective response to NEB may be exploited to improve the production and nutritional properties of milk. In the long term, it may extend dairy cows’ productive life and increase lifetime yield.


2009 ◽  
Vol 57 (1) ◽  
pp. 139-146
Author(s):  
Andrea Győrffy ◽  
Mónika Keresztes ◽  
Vera Faigl ◽  
Vilmos Frenyó ◽  
Margit Kulcsár ◽  
...  

In the regulation of energy metabolism, the liver plays an important role in the reinforcement of energy production. In periparturient cows the energy homeostasis turns into a negative energy balance that may shift the physiological regulation of energy balance towards pathological processes. Propylene glycol (PG), as a complementary source of energy used in the nutrition of dairy cows, alters systemic thyroid hormone economy; however, the exact mechanism through which highly glycogenic feed supplements impact liver metabolism is little known. Previous studies showed that only leptin receptors are expressed in the liver of cows, and now we report that leptin mRNA is expressed in the liver of cows as well. The present results show that the mRNA of leptin and its receptors are differentially modulated by the increased energy content of the feed consumed. Simultaneous changes in hepatic type I deiodinase activity suggest that hepatic modulation of the leptin system by PG supplementation may be mediated by an increased local thyroxine-triiodothyronine conversion. Since PG supplementation with simultaneous T4–T3 turnover and increased hepatic leptin- and short-form leptin receptor mRNA were not associated with a significant change in hepatic total lipid levels, it is suggested that the leptin system, directly or indirectly modulated by thyroid hormones, may represent a local defence mechanism to prevent fatty liver formation.


2021 ◽  
pp. 2392-2396
Author(s):  
Sumpun Thammacharoen ◽  
Sapon Semsirmboon ◽  
Somchai Chanpongsang ◽  
Narongsak Chaiyabutr ◽  
Pawares Panyasomboonying ◽  
...  

Background and Aim: Metabolism and environment are closely related. Under high ambient temperature (HTa), dairy cows may have different energy metabolism during summer and winter. The present study was carried out to investigate the effect of HTa on the milk yield and blood concentration of beta-hydroxybutyrate (BHBA) and glucose at the herd level. Materials and Methods: One large dairy farm in Thailand with more than 100 crossbred Holstein cows milked each month was selected. The first experiment was performed on non-lactating cows to determine the normal daily concentrations of blood BHBA and glucose. Under the HTa condition, there was no significant change in blood BHBA and glucose concentrations. The second experiment was performed using a prospective cohort clinical design to demonstrate the seasonal effect on milk yield and blood BHBA as an indication of energy metabolism at the herd level. Results: The temperature and humidity index for the winter (78.1±0.5) and summer (83.4±0.7) periods differ significantly. The average milk yield during the winter period was 17.8% higher than during the summer period. The reduction of body condition score (BCS) during early lactation was significant in the winter cows. Both higher milk yield and lower BCS in the winter cows suggested a state of negative energy balance. However, there was no difference in blood BHBA and glucose concentrations between winter and summer cows. The effect of HTa on insulin signaling appeared to be a counterbalancing factor for the ketogenic status. Based on the present results, it would be interesting to further investigate the incidence of subclinical and clinical ketosis in a dairy farm under tropical conditions. Conclusion: The present experiment revealed that HTa during summer decreased milk yield in dairy cows fed under tropical conditions. Higher milk yield in winter caused a greater reduction of BCS and suggested a greater negative energy balance. However, there was no seasonal effect on blood BHBA and glucose concentrations.


2001 ◽  
Vol 2001 ◽  
pp. 215-215 ◽  
Author(s):  
D.R. Mackey ◽  
A.R.G. Wylie ◽  
J.F. Roche ◽  
J.M. Sreenan ◽  
M.G. Diskin

Severe negative energy balance (NEB) in the postpartum period of dairy cows may be associated with declining fertility but the mechanisms by which nutrition influences reproduction are complex, poorly understood and confounded by lactation. Hence, both chronic and acute nutritional restriction of beef heifers have been used as models to examine the effects of NEB on ovarian and endocrine responses in the absence of lactation. Plasma IGF-I concentrations gradually decreased until the onset of anoestrus (Stagg et al., 1999) but concentrations may be confounded with stage of the oestrous cycle, especially around ovulation (Mackey et al., 2000). Therefore, the aim of this study was to examine the effect of nutritional restriction on periovulatory oestradiol (E2) and IGF-I concentrations.


2001 ◽  
Vol 26 (1) ◽  
pp. 223-236 ◽  
Author(s):  
M. C. Lucy ◽  
B. A. Crooker

AbstractSelection of dairy cattle for increased milk production has decreased some indices of reproductive efficiency. For example, days open are increased by one day for every 100 kg of increased milk yield per lactation. Some of the change in days open can be explained by delayed onset of oestrous cyclicity and lower conception rate to artificial insemination in cows with greater milk production. Despite these negative associations between milk production and reproduction, reproduction in herds of high producing dairy cattle is not necessarily compromised relative to reproduction in herds of low producing dairy cattle. This is because there is a large environmental effect on dairy reproduction. High producing herds generally have better management and better oestrous detection. Therefore, high producing dairy herds may partially overcome the antagonistic relationship between milk production and reproduction. Physiological mechanisms that lead to poorer reproduction in high producing cows are partially defined. Negative energy balance that occurs in high producing dairy cows can be associated with a delay in the initiation of ovarian cycles and the interval to first breeding. Many of the effects of negative energy balance on postpartum reproduction can be explained by decreased serum luteinizing hormone (LH) that is associated with negative energy balance. Serum LH increases as cows move toward positive energy balance and greater LH stimulates growth and ovulation of ovarian follicles. We have initiated studies to address physiological differences in high and low index dairy cows. The reproductive endocrinology of cows from a control line (5,900 kg milk/lactation) and a select line (10,900 kg milk/lactation) of dairy cows at the University of Minnesota was studied over a two-year period. Cows in Year 1 were similar for serum concentrations of LH, follicle stimulating hormone (FSH), and oestradiol (preovulatory period). In both years, serum concentrations of progesterone during luteal phases, however, were decreased in select cows. The Year 2 cows also had a delay in the return to oestrous cyclicity that was associated with reduced LH. The possibility that decreased progesterone causes infertility in dairy cows will require further study. Collectively, these data suggest that changes in blood progesterone concentrations may explain, partially, lower fertility in high index dairy cows.


2016 ◽  
Vol 99 (12) ◽  
pp. 10009-10021 ◽  
Author(s):  
G. Andres Contreras ◽  
Kyan Thelen ◽  
Sarah E. Schmidt ◽  
Clarissa Strieder-Barboza ◽  
Courtney L. Preseault ◽  
...  

2001 ◽  
Vol 26 (1) ◽  
pp. 133-145 ◽  
Author(s):  
W.R. Butler

AbstractIncreased genetic potential for milk production has been associated with a decline in fertility of lactating cows. Following parturition the nutritional requirements increase rapidly with milk production and result in negative energy balance (NEBAL). NEBAL delays the time of first ovulation thereby affecting ovarian cycles before and during the subsequent breeding period The effects of NEBAL on reinitiation of ovulation are manifested through inhibition of LH pulse frequency and low levels of glucose, insulin and IGF-I in blood that collectively restrain oestrogen production by dominant follicles. Upregulation of LH pulses and peripheral IGF-I in association with the NEBAL nadir increases the likelihood that emerging dominant follicles will ovulate. The legacy of NEBAL is reduced fertility after insemination in conjunction with reduced serum progesterone concentrations. Diets high in crude protein support high milk yield, but may be detrimental to reproductive performance. Depending upon protein quantity and composition, serum concentrations of progesterone may be lower and the uterine luminal environment is altered. High protein intake is correlated with plasma urea concentrations that are inversely related to uterine pH and fertility. The direct effects of high dietary protein and plasma urea on embryo quality and development in cattle are inconsistent. In conclusion, the poor fertility of high producing dairy cows reflects the combined effects of a uterine environment that is dependent on progesterone, but has been rendered suboptimal for embryo development by antecedent effects of negative energy balance and may be further compromised by the effects of urea resultingfrom intake of high dietary protein.


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