Search

Elevated levels of NEFA caused by negative energy balance in transition cows induce cellular dyshomeostasis. Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) can maintain cellular homeostasis and act as a critical regulator of stress responses besides functioning in the ubiquitin-like system. The objective of this study was to elucidate the UFL1 working mechanism on promoting cellular adaptations in bovine mammary epithelial cells (BMECs) in response to NEFA challenge, with an emphasis on the ER and mitochondrial function. The results showed that exogenous NEFA and UFL1 depletion resulted in the disorder of ER and mitochondrial homeostasis and the damage of BMEC integrity, overexpression of UFL1 effectively alleviated the NEFA-induced cellular dyshomeostasis. Mechanistically, our study found that UFL1 had a strong interaction with IRE1α and could modulate the IRE1α/XBP1 pathway of unfolded protein response in NEFA-stimulated BMECs, thereby contributing to the modulation of cellular homeostasis. These findings imply that targeting UFL1 may be a therapeutic alternative to relieve NEB-induced metabolic changes in perinatal dairy cows. [Display omitted] • NEFA and UFL1 depletion resulted in the disorder of ER and mitochondrial homeostasis. • UFL1 overexpression effectively alleviated the NEFA-induced cellular dyshomeostasis. • UFL1 could interact with IRE1α and modulate the IRE1α/XBP1 pathway of UPR in BMECs. • IRE1α functioned as a positive regulator in MAMs homeostasis of NEFA-induced BMECs. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effects of heat stress on 30 Saanen goats of different ages (young, middle-aged, and old). The average temperature and humidity values during the trial were 27.82 °C and 40.65%, respectively. Statistically significant differences in pulse rate (PR), respiratory rate (SS), and temperature humidity index (THI) were found between months (P < 0.05). Beta-hydroxybutyric acid (BHBA) values were found to be statistically significant in the young and middle-aged group (P < 0.05), with the highest in the middle-aged group obtained in June (0.65 mmol/L). Non-esterified fatty acids (NEFA) and urea (BUN) were significantly different (P < 0.05) in all age groups, whereas creatinine values showed no significant differences between groups. Significant positive relationships were found between body weight (BW) and body condition score (BCS), as well as pulse rate (PR) and daily average daily milk yield (DAMY) (P < 0.01). A positive correlation was also found between the respiratory rate (SS) and pulse rate (P < 0.01). As a result, although attempts have been made to prevent the decrease in productivity with applications for animals under heat stress, the optimal strategy may be to address the source of the problem. Issues that cause heat accumulation in the body should be identified and necessary arrangements should be made in the shelter to distribute heat to ensure that animals are less affected. Shaded areas should be provided in cases of stress caused by heat. An appropriate structural arrangement for temperature, humidification, and ventilation systems, as well as the provision of abundant fresh drinking water, would also be beneficial.Highlights: Decreased milk yield is related to thyroid hormones which speed up metabolic processes by increasing enzyme activity. A significant decrease in milk yield was observed in both the young and old groups in July and August, when heat stress was most prevalent. The middle-aged group was least affected by heat stress in terms of milk yield. Changes in creatinine levels were insignificant, only determining a significant decrease in urea levels. Despite decreased feed intake, no rise in plasma NEFA was observed. [ABSTRACT FROM AUTHOR]

During the gestation and lactation period, the energy demand in pregnant and lactating bitches is elevated. Non‐esterified fatty acids (NEFAs) are utilized either directly from the fed diet or from body fat storage. High NEFA concentration in the blood plasma leads to an increased risk for diseases. Therefore, measuring blood NEFA concentrations may be an indicator for a period of scarcity. The aim of this study is to explore if serum NEFA concentrations in healthy bitches change during gestation and lactation. Healthy pregnant and lactating bitches were sampled on three appointed dates around parturition. NEFA values were examined with a multiparameter clinical chemistry analyser. All statistical analyses were performed using R. Overall, 38 bitches were enrolled in the study. Twenty‐one bitches were sampled on all three appointed dates. The median NEFA concentration antepartum was 0.73 mmol/L (IQR: 0.59, 1.01); during peak lactation, it was 0.57 mmol/L (IQR: 0.44, 0.82); and around weaning, it was 0.58 mmol/L (IQR: 0.46, 0.73). NEFA concentrations rose slightly with litter size in late gestation. Body condition score had no influence on observed NEFA values. We conclude that NEFA concentrations widely remain within reference ranges in well‐fed pregnant and lactating bitches. Nevertheless, they may be a valuable parameter to assess the actual metabolic status of malnourished pregnant and lactating bitches. [ABSTRACT FROM AUTHOR]

This narrative review explores the pathophysiology of obesity, cellular senescence, and exosome release. When exposed to excessive nutrients, adipocytes develop mitochondrial dysfunction and generate reactive oxygen species with DNA damage. This triggers adipocyte hypertrophy and hypoxia, inhibition of adiponectin secretion and adipogenesis, increased endoplasmic reticulum stress and maladaptive unfolded protein response, metaflammation, and polarization of macrophages. Such feed-forward cycles are not resolved by antioxidant systems, heat shock response pathways, or DNA repair mechanisms, resulting in transmissible cellular senescence via autocrine, paracrine, and endocrine signaling. Senescence can thus affect preadipocytes, mature adipocytes, tissue macrophages and lymphocytes, hepatocytes, vascular endothelium, pancreatic β cells, myocytes, hypothalamic nuclei, and renal podocytes. The senescence-associated secretory phenotype is closely related to visceral adipose tissue expansion and metaflammation; inhibition of SIRT-1, adiponectin, and autophagy; and increased release of exosomes, exosomal micro-RNAs, pro-inflammatory adipokines, and saturated free fatty acids. The resulting hypernefemia, insulin resistance, and diminished fatty acid β-oxidation lead to lipotoxicity and progressive obesity, metabolic syndrome, and physical and cognitive functional decline. Weight cycling is related to continuing immunosenescence and exposure to palmitate. Cellular senescence, exosome release, and the transmissible senescence-associated secretory phenotype contribute to obesity and metabolic syndrome. Targeted therapies have interrelated and synergistic effects on cellular senescence, obesity, and premature aging. [ABSTRACT FROM AUTHOR]

Periparturient period is the most important and critical period in the life of dairy cows, as various alterations are seen in physiological and hormonal mechanism of dairy animals during this period due to which there is development of Negative energy balance in the body of animal resulting in various metabolic diseases in the animals. So for preventing these diseases it is important to predict these diseases well in advance. In order to predict these diseases, various prediction equations were created by using the values obtained from various metabolic parameters from the healthy and diseases animal during the periparturient period. [ABSTRACT FROM AUTHOR]

Simple Summary: Ketosis in cows occurs when excessive ketone bodies are produced by the liver, typically due to energy deficits from reduced feed intake or specific dietary conditions. Scientists have noticed that cows with ketosis have lower amounts of a substance named L-histidine. This sparked curiosity about how L-histidine might help cows with this problem. To understand this better, researchers looked at changes in cow mammary cells caused by the fat and whether L-histidine could help. They found many changes in the cell's substances, some increasing and some decreasing, showing that the cells were trying to respond to the fat. Interestingly, when L-histidine was added, it seemed to help by changing some of these substances, suggesting it might protect the cells. One particular substance seemed to play a big role and was affected by both the fat and L-histidine in different ways. This research helps us understand the complicated ways cow cells react to excess fat and suggests that L-histidine could be a helpful tool in keeping cows healthy, which is valuable for farmers and the dairy industry. Non-esterified fatty acids (NEFAs) are pivotal in energy metabolism, yet high concentrations can lead to ketosis, a common metabolic disorder in cattle. Our laboratory observed lower levels of L-histidine in cattle suffering from ketosis, indicating a potential interaction between L-histidine and NEFA metabolism. This relationship prompted us to investigate the metabolomic alterations in bovine mammary epithelial cells (BMECs) induced by elevated NEFA levels and to explore L-histidine's potential mitigating effects. Our untargeted metabolomic analysis revealed 893 and 160 metabolite changes in positive and negative models, respectively, with VIP scores greater than 1 and p-values below 0.05. Notable metabolites like 9,10-epoxy-12-octadecenoic acid were upregulated, while 9-Ethylguanine was downregulated. A pathway analysis suggested disruptions in fatty acid and steroid biosynthesis pathways. Furthermore, L-histidine treatment altered 61 metabolites in the positive model and 34 in the negative model, with implications for similar pathways affected by NEFA. Overlaying differential metabolites from both conditions uncovered a potential key mediator, 1-Linoleoylglycerophosphocholine, which was regulated in opposite directions by NEFA and L-histidine. Our study uncovered that both NEFA L- and histidine metabolomics analyses pinpoint similar lipid biosynthesis pathways, with 1-Linoleoylglycerophosphocholine emerging as a potential key metabolite mediating their interaction, a discovery that may offer insights for therapeutic strategies in metabolic diseases. [ABSTRACT FROM AUTHOR]

Aims: Currently, there is little and inconsistent evidence regarding the possible adverse effects of circulating levels of non-esterified fatty acids (NEFA) on kidney function decline in patients with type 2 diabetes mellitus (T2DM). Methods: We followed for a median of 4.6 years 85 post-menopausal women with non-insulin-treated T2DM and preserved kidney function at baseline. Serum NEFA concentrations were measured using an enzymatic colorimetric method. Glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results: Enrolled patients had a baseline mean eGFRCKD-EPI of 83 ± 12 mL/min/1.73 m2 and a median serum NEFA concentration of 662 uEq/L (interquartile range 524–842 uEq/L). During the follow-up period, 13 patients developed kidney function decline at follow-up (defined as an eGFRCKD-EPI decline ≥ 30% from baseline). In Cox proportional hazards regression analyses, higher serum NEFA levels were significantly associated with an increased risk of developing kidney function decline (adjusted-hazard ratio 3.67, 95% CI 1.64–8.22, p < 0.001; for each 1-SD increment, i.e., 262 uEq/L), even after adjustment for waist circumference, hemoglobin A1c, C-reactive protein, HOMA-estimated insulin resistance, hypertension, dyslipidemia, microalbuminuria, baseline eGFRCKD-EPI, as well as temporal changes in HbA1c levels or the use of renin-angiotensin system inhibitors over the follow-up. Conclusions: The findings of this exploratory prospective study show that in post-menopausal women with T2DM and preserved kidney function at baseline, higher circulating levels of NEFA were strongly associated with a faster kidney function decline, even after adjustment for established renal risk factors and potential confounders. [ABSTRACT FROM AUTHOR]

ABSTRACT: Chromium (Cr) has been reported to modulate blood biochemistry in dairy cows. However, there is a discrepancy in the literature regarding the effects of dietary Cr supplementation on various blood parameters. This meta-analysis aimed to evaluate the effects of Cr supplementation in dairy cows on blood glucose, insulin, glucagon, nonesterified fatty acid (NEFA), cortisol, and serum total protein (STP) concentrations. Following relevant literature data extraction, a 3-level meta-analytical random effect model was fitted to the data expressed as standardized mean difference (SMD) of outcome measures of control versus Cr-supplemented cows (i.e., difference in mean between control and treatment group or pooled standard deviation). The SMD can be categorized as having a small effect (0.20), a moderate effect (0.50), and a large effect (0.80). The meta-regression identified the potential sources of heterogeneity, including the body weight of cows, experimental duration/duration of Cr supplementation, blood sampling time (3 wk before parturition until 4 wk after parturition categorized as the transition period, else as the nontransition period), and form of Cr complexes. Blood glucose did not differ significantly between control and Cr-supplemented cows with an estimated SMD of μ = 0.0071 (95% confidence interval [CI]: −0.212 to 0.226). The effect of Cr supplementation on blood insulin was also nonsignificant with an SMD of μ = 0.0007 (95% CI: −0.191 to 0.193). Cows receiving Cr supplements had significantly higher levels of glucagon than controls (95% CI: 0.116 to 0.489), with an estimated SMD = 0.303. Combined transition and nontransition data suggest Cr supplementation did not affect the concentration of NEFA. However, in transition cows, Cr supplementation significantly decreased blood NEFA levels as compared with controls (95% CI: −0.522 to −0.0039), with estimated SMD = −0.263. The estimated SMD was μ = −0.1983 (95% CI: −0.734 to 0.337) for cortisol and −0.0923 (95% CI: −0.316 to 0.131) for total protein. In summary, Cr supplementation in the transition cows decreased NEFA concentration. Blood glucose, insulin, cortisol, and STP concentrations were unaffected. However, Cr supplementation increased glucagon concentration.

Ketosis is widespread disturbance among dairy cows, causing significant economic losses and requiring further study of its pathogenesis. This particularly applies to less traditional dairy breeds, including the Brown Swiss. The aim of the study was to investigate the biochemical indicators in the Brown Swiss breed cows of different age at a stage with prevalent ketosis. The research was conducted on a dairy cow herd with a ketosis level exceeding 30%. Blood samples were collected from primiparous cows and cows in their 2nd-3rd lactation 5-7 days before calving (group BC), post calving 2-3 days (group 2-3 PC), and 7-10 days (group 7-10 PC). Biochemical indicators of blood serum aimed at determining the level of lipomobilization, ketone bodies, and liver function were determined using an automatic biochemical analyzer. In the group of primiparous cows 2-3 PC, there was an increase in the content of beta-hydroxybutyrate by 1.83 times, and ketonemia was observed in 40% of cows. The postpartum period in primiparous cows was accompanied by an increase non-esterified fatty acids concentration by 1.75-2 times. The level of AST was the lowest in the serum of gestating cows several days before calving, whereas after calving, an increase was observed. It was discovered that each group had animals with AST levels above 100 U/L. There were 20 % of animals in the 5-7 pre-calving group, and 80% in the 7-10 post-calving group. The level of total bilirubin in the group of primiparous cows 2-3 PC exceeded the level BC by 3.14 times, and in the group 7-10 post-calving by 2.67 times. In the BC group, 20% of cows during their 2nd-3rd lactation were found to have ketonemia, with beta-hydroxybutyrate level 1.43 mmol/L in the serum. The highest level of ketone bodies was detected in cows from the group 2-3 PC, with 60% showing subclinical and 20% showing clinical ketosis. Similarly to primiparous cows, cows in their 2nd-3rd lactation exhibited the development of negative energy balance in the postpartum period. In the group of cows BC, AST activity exceeded 100 U/L in 20% of animals, while in the groups 2-3 PC and 7-10 PC, the number of such animals reached 60%. These changes were accompanied by hyperbilirubinemia, which was observed after calving in 80% of cows in both groups. Therefore, an increase non-esterified fatty acids levels was observed in the postpartum period in primiparous cows and cows in their 2nd-3rd lactation of the Brown Swiss breed. The results indicate the development of lipomobilization syndrome. The most pronounced signs of ketosis development were observed in primiparous cows on days 7-10 after calving, while in multiparous cows, it was detected on days 2-3. The development of negative energy balance led to signs of liver damage characteristic of lipidosis - an increase in total bilirubin levels and, to a lesser extent, AST activity. Biochemical index changes during post-calving period were observed in primiparous cow with more prominent level. However, during late dry period metabolic disorders were detected in multiparous cow in which observed ketonemia.

This review presents evidence related to the postprandial responses after consumption of dairy products focusing on the effect of the dairy matrix and lipid response, which was also presented as part of a speech at the Nutrition Society Winter Conference, January 2023. The key findings are that the dairy product(s) that differentiate from others in the postprandial TAG response are products with a semi-solid structure. There were no differences in lipid responses between cheese and butter. The main factors viscosity, fat globule size and milk fat globule membrane do not seem to explain the effect of the dairy matrix in the acute postprandial response. In summary, it is very difficult to investigate the effects of the dairy matrix per see and with the few studies conducted to date, no clear cause and effect can be established. Future research should focus on the semi-solid dairy matrix, and studies investigating specifically the yoghurt matrix are warranted. [ABSTRACT FROM AUTHOR]

Chromium (Cr) has been reported to modulate blood biochemistry in dairy cows. However, there is a discrepancy in the literature regarding the effects of dietary Cr supplementation on various blood parameters. This meta-analysis aimed to evaluate the effects of Cr supplementation in dairy cows on blood glucose, insulin, glucagon, nonesterified fatty acid (NEFA), cortisol, and serum total protein (STP) concentrations. Following relevant literature data extraction, a 3-level meta-analytical random effect model was fitted to the data expressed as standardized mean difference (SMD) of outcome measures of control versus Cr-supplemented cows (i.e., difference in mean between control and treatment group or pooled standard deviation). The SMD can be categorized as having a small effect (0.20), a moderate effect (0.50), and a large effect (0.80). The meta-regression identified the potential sources of heterogeneity, including the body weight of cows, experimental duration/duration of Cr supplementation, blood sampling time (3 wk before parturition until 4 wk after parturition categorized as the transition period, else as the nontransition period), and form of Cr complexes. Blood glucose did not differ significantly between control and Cr-supplemented cows with an estimated SMD of μ = 0.0071 (95% confidence interval [CI]: −0.212 to 0.226). The effect of Cr supplementation on blood insulin was also nonsignificant with an SMD of μ = 0.0007 (95% CI: −0.191 to 0.193). Cows receiving Cr supplements had significantly higher levels of glucagon than controls (95% CI: 0.116 to 0.489), with an estimated SMD = 0.303. Combined transition and nontransition data suggest Cr supplementation did not affect the concentration of NEFA. However, in transition cows, Cr supplementation significantly decreased blood NEFA levels as compared with controls (95% CI: −0.522 to −0.0039), with estimated SMD = −0.263. The estimated SMD was μ = −0.1983 (95% CI: −0.734 to 0.337) for cortisol and −0.0923 (95% CI: −0.316 to 0.131) for total protein. In summary, Cr supplementation in the transition cows decreased NEFA concentration. Blood glucose, insulin, cortisol, and STP concentrations were unaffected. However, Cr supplementation increased glucagon concentration. [ABSTRACT FROM AUTHOR]

This research was to study the effect of adding glycerol at different levels (T1 = control treatment without glycerol, T2 = 75 ml and T3 = 150 ml glycerol) in the body weight, body measurements and some blood characteristics of Holstein calves from 60 to 120 days of calves age. Body weight increased (P≤0.05) in T3 calves at 80 and 100 days of age, also body weight increased in T2 and T3 calves at 120 days of age. T2 calves were significantly superior (P≤0.01) in average total gains from 60 to 120 days of age. Significantly increased (P≤0.05) at the ages of 100 and 120 days of: Wither height in T3 calves, Body length in T2 calves and Heart girth in T2 and T3 calves. Blood glucose concentration increased (P≤0.05) and blood NEFA concentration decreased (P≤0.01) in T2 calves at 80 days of age. At the age of 100 and 120 days, the concentration of blood glucose was increased (P≤0.01 and P≤0.05) and the concentration of NEFA and BHBA decreased (P≤0.01) in calves of the two treatments T2 and T3. We conclude that the addition of glycerol (75 and 150 ml/day) in the feeding of calves increases body weight, promotes growth and improves blood characteristics by increasing blood glucose and reducing NEFA and BHBA concentrations. [ABSTRACT FROM AUTHOR]

Copyright of Iranian Veterinary Journal is the property of Shahid Chamran University of Ahvaz and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background High concentrations of NEFA relative to a defined reference or ‘cut‐point’ values before calving can predict the risk of specific or collective periparturient disease events. Objectives A field‐based cohort study was conducted to evaluate the value and critical points of serum nonesterified fatty acids (NEFA) at the precalving time to predict the occurrence of postpartum diseases and reproductive performance in dairy cows. Methods Blood samples were taken from 521 high‐yielding dairy cows at 1 week (±3 days) before calving and NEFA levels were measured. Health and reproduction information of each cow includes dystocia, retained placenta, milk fever, metritis, mastitis, pregnancy in the first insemination and pregnancy in the first two inseminations, and culling in the first 60 days of lactation and milk production. Results Our results show that there are significant relationships between precalving NEFA with the probability of pregnancy at the first and the first two inseminations after calving. The cows that had NEFA concentrations less than 0.5 mmol/L at the last week of pregnancy were 3.51 and 3.15 times more likely to be pregnant at first insemination and the first two inseminations, respectively. Also, our results showed that there are significant relationships between precalving NEFA concentration and the likelihood of dystocia and milk fever. The probability of dystocia and milk fever occurrence were 2.56 and 1.91 times greater in those cows that had NEFA concentrations more than 0.3 mmol/L, respectively. Conclusions The present results indicated that Increasing NEFA during the prepartum period could adversely affect the reproductive efficiency of dairy cows.

The aim of this study was to investigate the effect of adding glycerol at different levels (T1 = control treatment without glycerol, T2 = 75 ml and T3 = 150 ml glycerol) on daily milk yield, milk components and some blood parameters of Holstein cows during the period of 60 days. Milk yield increased significantly (P≤0.05) at 15th day of the experiment, and highly significant (P≤0.01) at 30th and 60th days of the experiment in T3 group. Percentage of milk protein and lactose increased (P≤0.01) in T2 and T3 groups and the percentage of milk fat in the T3 group decreased at day 60 of the experiment. The blood glucose concentration increased (P≤0.01) in T2 and T3 groups at 30 and 60 days of the experiment. Triglyceride concentration increased (P≤0.01) in the blood of T2 and T3 treated cows at day 60. The concentration of cholesterol, NEFA and BHBA decreased (P≤0.01) in T3 treated cows at day 60 of the experiment. The concentration of phosphorous and magnesium were also affected as a result of glycerol treatment. It can be concluded that the addition of dietary glycerol 150 ml / day enhanced milk yield, protein and lactose percentage, and improved blood parameters by increasing blood glucose and reducing NEFA and BHBA concentrations of Holstein cows. [ABSTRACT FROM AUTHOR]

Simple Summary: The productivity and survival of females in the rabbit industry depends largely on the correct management of their body reserves. This management includes both their body condition and the mobilization of their body reserves during high energy demand or critical moments for reproduction, such as mating, gestation, or delivery. In this work, a study of body weight, perirenal fat thickness, non-esterified fatty acid concentration, and leptin concentration at these key moments, when a semi-intensive reproductive rhythm is applied, is carried out. This detailed knowledge is decisive to optimising the productivity of females. The aim of this work is to study changes in body weight, perirenal fat thickness (PFT), and non-esterified fatty acid (NEFA) and leptin concentrations throughout the reproductive life of the rabbit female and their correlations when a semi-intensive reproductive rhythm is applied. A total of 46 lactating females were used. Body weight, PFT, and NEFA and leptin concentration were recorded at 12 weeks of age, at first mating and delivery, and at second, third, and fourth mating, 12th d of gestation, and delivery. The highest body weight was detected on the 12th d of any gestation, around 4280 g, and the lowest weight was at delivery, around 4030 g. PFT increased until third mating. NEFA and leptin concentration showed a cyclical pattern throughout the reproductive lifespan of the females. NEFAs presented the highest concentration at delivery within each reproductive cycle and levels decreased over the course of the deliveries (0.423 mmol/L at first delivery, 0.406 mmol/L at second delivery, 0.371 mmol/L at third delivery, and 0.309 mmol/L at fourth delivery). Similar NEFA concentrations at mating and on the 12th d of gestation were obtained. Leptin showed the highest concentrations at mating within each reproductive cycle. Leptin decreased between mating and delivery in all reproductive cycles and it was close to 1 ng/mL HE. Low or null correlations were shown between body weight, PFT, and NEFA and leptin concentration at mating, 12th d of gestation, and delivery. In conclusion, females are able to maintain a semi-intensive reproductive rhythm across four parities weighing around 4 kg from first mating. Females had an increased perirenal fat thickness until third delivery, and their NEFA concentration was maximum at delivery and leptin concentration was maximum at mating. Body weight, PFT, and NEFA and leptin concentration should be measured during critical moments of reproductive life in order to determine body condition and energy mobilization, due to their low or null correlations. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the influence of postpartum drenching with a feed additive on the plasma concentration of biochemical parameters while factoring in prepartum rumination times (RT). One hundred and sixty-one cows were fitted with a Ruminact© HR-Tag approximately 5 days before calving. Drenching and control groups were established based on calving dates. Animals in the drenched group were treated three times (Day 1/day of calving/, Day 2, and Day 3 postpartum) using a feed additive containing calcium propionate, magnesium sulphate, yeast, potassium chloride and sodium chloride mixed in approximately 25 L of lukewarm tap water. Blood samples were collected on Days 1, 2, 3, 7 and 12. Cows with below the average RT were categorised as "low rumination" and those above it as "high rumination" animals. Drenching decreased the plasma concentrations of total protein, urea and creatinine and increased the levels of alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and chloride. Low rumination time prepartum resulted in higher concentrations of beta-hydroxybutyrate, total protein and activities of alkaline phosphatase and GGT, while it decreased the activity of ALT and the concentrations of calcium, magnesium, sodium and potassium. The day of lactation had an effect on all parameters except for potassium. [ABSTRACT FROM AUTHOR]

Abstract Background High serum NEFA and GDF-15 are risk factors for CAD and have been linked to detrimental cardiovascular events. It has been hypothesized that hyperuricemia causes CAD via the oxidative metabolism and inflammation. The current study sought to clarify the relationship between serum GDF-15/NEFA and CAD in individuals with hyperuricemia. Methods Blood samples collected from 350 male patients with hyperuricemia(191 patients without CAD and 159 patients with CAD, serum UA > 420 μmol/L) to measure serum GDF-15 and NEFA concentrations with baseline parameters. Results Serum circulating GDF-15 concentrations(pg/dL) [8.48(6.67,12.73)] and NEFA levels(mmol/L) [0.45(0.32,0.60)] were higher in hyperuricemia patients with CAD. Logistic regression analysis revealed that the OR (95% CI) for CAD were 10.476 (4.158, 26.391) and 11.244 (4.740, 26.669) in quartile 4 (highest) respectively. The AUC of the combined serum GDF-15 and NEFA was 0.813 (0.767,0.858) as a predictor of whether CAD occurred in male with hyperuricemia. Conclusions Circulating GDF-15 and NEFA levels correlated positively with CAD in male patients with hyperuricemia and measurements may be a useful clinical adjunct.

Non-esterified fatty acids (NEFAs) are pivotal in energy metabolism, yet high concentrations can lead to ketosis, a common metabolic disorder in cattle. Our laboratory observed lower levels of L-histidine in cattle suffering from ketosis, indicating a potential interaction between L-histidine and NEFA metabolism. This relationship prompted us to investigate the metabolomic alterations in bovine mammary epithelial cells (BMECs) induced by elevated NEFA levels and to explore L-histidine’s potential mitigating effects. Our untargeted metabolomic analysis revealed 893 and 160 metabolite changes in positive and negative models, respectively, with VIP scores greater than 1 and p-values below 0.05. Notable metabolites like 9,10-epoxy-12-octadecenoic acid were upregulated, while 9-Ethylguanine was downregulated. A pathway analysis suggested disruptions in fatty acid and steroid biosynthesis pathways. Furthermore, L-histidine treatment altered 61 metabolites in the positive model and 34 in the negative model, with implications for similar pathways affected by NEFA. Overlaying differential metabolites from both conditions uncovered a potential key mediator, 1-Linoleoylglycerophosphocholine, which was regulated in opposite directions by NEFA and L-histidine. Our study uncovered that both NEFA L- and histidine metabolomics analyses pinpoint similar lipid biosynthesis pathways, with 1-Linoleoylglycerophosphocholine emerging as a potential key metabolite mediating their interaction, a discovery that may offer insights for therapeutic strategies in metabolic diseases.

The current research aimed to assess apoptotic cell ratio (ACR) via TUNEL staining in bovine embryos produced in vitro from oocytes matured in stressful conditions of elevated concentrations of non-esterified fatty acids (NEFAs). The maturation conditions in the current study were resemble the situation in the oocyte microenvironment of metabolically stressed lactating dairy cows during the post-partum period where the negative energy balance occurred. Oocytes were in vitro matured under elevated levels of NEFAs for 24 h in serum-free maturation media. Obtained zygotes were cultured in synthetic oviduct fluid with 5% FCS for eight days. Blastocyst stages from each treatment group were assessed and evaluated for their quality by determining the ACR by means of TUNEL staining. The presence of palmitic or stearic acid at high concentrations during oocyte maturation increased ACR, whereas oleic acid had no significant effects. The results of the present study concluded that compromised oocyte microenvironment by metabolic stressor such as high NEFAs concentrations which is the situation during the negative energy balance that are happened post-partum in dairy cows could decrease the quality of preimplantation embryos as indicated by the incidence of apoptosis. [ABSTRACT FROM AUTHOR]

Background: High concentrations of NEFA relative to a defined reference or 'cut‐point' values before calving can predict the risk of specific or collective periparturient disease events. Objectives: A field‐based cohort study was conducted to evaluate the value and critical points of serum nonesterified fatty acids (NEFA) at the precalving time to predict the occurrence of postpartum diseases and reproductive performance in dairy cows. Methods: Blood samples were taken from 521 high‐yielding dairy cows at 1 week (±3 days) before calving and NEFA levels were measured. Health and reproduction information of each cow includes dystocia, retained placenta, milk fever, metritis, mastitis, pregnancy in the first insemination and pregnancy in the first two inseminations, and culling in the first 60 days of lactation and milk production. Results: Our results show that there are significant relationships between precalving NEFA with the probability of pregnancy at the first and the first two inseminations after calving. The cows that had NEFA concentrations less than 0.5 mmol/L at the last week of pregnancy were 3.51 and 3.15 times more likely to be pregnant at first insemination and the first two inseminations, respectively. Also, our results showed that there are significant relationships between precalving NEFA concentration and the likelihood of dystocia and milk fever. The probability of dystocia and milk fever occurrence were 2.56 and 1.91 times greater in those cows that had NEFA concentrations more than 0.3 mmol/L, respectively. Conclusions: The present results indicated that Increasing NEFA during the prepartum period could adversely affect the reproductive efficiency of dairy cows. [ABSTRACT FROM AUTHOR]

The associations between early lactation changes in the body condition score (BCS) and mid‐lactation levels of blood insulin‐like Growth Factor‐I (IGF‐1), prolactin, insulin, nonesterified fatty acids (NEFA), milk production and some reproductive indices were investigated. Monthly milk yield and BCS were recorded. Blood samples were collected on days 60, 90, and 120 (±5 days) of lactation. Twelve and 17 cows showed BCS losses ≤0.75 and >0.75 on day 60, respectively. BCS losses ≤0.75 till day 60 after calving enhanced the IGF‐I concentration on day 90 (57.8 ± 10.7 vs. 35.6 ± 17.8 ng/mL; p =.001). The differences in blood metabolites were prominent on day 90. Trends of insulin changes between day 60 BCS (p =.04) groups were different. Inverse correlations were detected between IGF‐I and NEFA (−0.6, p =.001), IGF‐I and milk production (−0.4, p =.05), NEFA and prolactin (−0.8, p <.001) on day 90. Higher percentages of cows with BCS loss >0.75 (day 60) showed their first heat after day 40 postpartum. In conclusion, irrespective of BCS at the time of breeding, the level of BCS loss during the first 60 days of lactation may affect further reproductive performance due to prolonged alterations of IGF‐I, NEFA, prolactin and insulin levels. The extent of postpartum BCS loss may be a predictor of the metabolic status of cows during mid‐lactation. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to determine the levels of various hormones and metabolites in the blood of Holstein dairy cows during the crucial transition period, 7 days before parturition and a further 14 and 21 days postparturition, exploring the link between pregnancy probability after first artificial insemination and during the first 100 days in milk. The cows were split into two subgroups, those that were diagnosed as pregnant and those that did not conceive after further attempts at artificial insemination. The results showed that the levels of IGF-1 and progesterone exhibited significant differences among the two subgroups, which could have a diagnostic value in predicting pregnancy. These findings are relevant for dairy farm management, as they provide new information about the hormones and metabolites that affect the health and reproductive performance of dairy cows. The purpose of this study was to determine the link between insulin-like growth factor 1 (IGF-1), progesterone (PROG), non-esterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and glucose (GLU) and pregnancy probability after the first artificial insemination (AI) and during the first 100 days in milk (DIM), during the critical transition period. We determined levels of serum IGF-1, PROG, NEFA, BHB, and GLU in Holstein dairy cows via ELISA, using blood samples collected 7 days before parturition (DAP) until 21 days postparturition (DPP). The group was split into cows diagnosed pregnant at 100 DIM (PREG) and those that did not conceive at 100 and 150 DIM (NPREG). Serum IGF-1 and PROG median levels at 7 DAP were significantly higher in PREG vs. NPREG (p = 0.029), the only statistically significant differences across the subgroups. At 7 DAP, IGF-1 levels within the initial group showed a strong negative correlation with PROG (r = −0.693; p = 0.006), while for the PREG subgroup, the IGF-1 levels exhibited a very strong positive correlation with GLU (r = 0.860; p = 0.011) and NEFA (r = 0.872; p = 0.013). IGF-1 and PROG levels detected at 7 DAP may be useful to predict pregnancy at 100 DIM. The positive correlation of NEFA and GLU levels during the transition period demonstrates that the initial group is not in NEB; thus, the NEFA level was not a decisive factor for reproduction success. [ABSTRACT FROM AUTHOR]

The aim of this study; The aim of this study is to examine the effects of glucose precursors on the negative energy balance problem seen in the transition period, on blood BHBA, NEFA and body condition score (BCS). In the study, 60 Holstein dairy cows with at least one birth were used. The animals were divided into 3 groups of 20 each. Animals in the glycerol (G) group were given 450 ml of glycerol with a pump once a day after morning feeding, and 300 ml of propylene glycol in the Propylene Glycol (PG) group. No application was made to the animals in the control (K) group. For metabolic profile tests such as beta hydroxy-butyric acid (BHBA) and non-esterified fatty acids (NEFA), blood samples were taken at prenatal 1, postnatal 0, 1, 2 and 3 weeks and analyzed with commercial kits. There was no difference between the groups in BHBA, NEFA and VKS levels from blood samples taken from cows. It was concluded that the using glucose precursor which are propylene glycol and glycerol during the transiiton period there was no significant effect on BHBA, NEFA and BCS in dairy cows. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyse the relationship between the body condition and the results of metabolic profile tests done in the milk (DIM) of dairy cows in different days. Moreover, critical points in the early pre- and postpartum period were also analysed. In the experiment, blood and urine samples were taken from 1984 clinically healthy cows (from 49 large scale dairy farms in Hungary), selected randomly from various groups of cows with different physiological stage of lactation and gestation, 3-5 hours after the morning feeding. During the experiment body condition scoring (BCS) was measured on 1-5 scale, as well. It was concluded, that the BCS (body condition score) decreased from the 1st day of lactation (3.48) onwards till the 44th day (2.65) and slightly increased till the day 218 (2.89). The haemoglobin value and the glucose concentration in blood samples were ranging within the physiological range and followed the tendency of BCS and the relationship between them and DIM was (P

The aim of this work is to study changes in body weight, perirenal fat thickness (PFT), and non-esterified fatty acid (NEFA) and leptin concentrations throughout the reproductive life of the rabbit female and their correlations when a semi-intensive reproductive rhythm is applied. A total of 46 lactating females were used. Body weight, PFT, and NEFA and leptin concentration were recorded at 12 weeks of age, at first mating and delivery, and at second, third, and fourth mating, 12th d of gestation, and delivery. The highest body weight was detected on the 12th d of any gestation, around 4280 g, and the lowest weight was at delivery, around 4030 g. PFT increased until third mating. NEFA and leptin concentration showed a cyclical pattern throughout the reproductive lifespan of the females. NEFAs presented the highest concentration at delivery within each reproductive cycle and levels decreased over the course of the deliveries (0.423 mmol/L at first delivery, 0.406 mmol/L at second delivery, 0.371 mmol/L at third delivery, and 0.309 mmol/L at fourth delivery). Similar NEFA concentrations at mating and on the 12th d of gestation were obtained. Leptin showed the highest concentrations at mating within each reproductive cycle. Leptin decreased between mating and delivery in all reproductive cycles and it was close to 1 ng/mL HE. Low or null correlations were shown between body weight, PFT, and NEFA and leptin concentration at mating, 12th d of gestation, and delivery. In conclusion, females are able to maintain a semi-intensive reproductive rhythm across four parities weighing around 4 kg from first mating. Females had an increased perirenal fat thickness until third delivery, and their NEFA concentration was maximum at delivery and leptin concentration was maximum at mating. Body weight, PFT, and NEFA and leptin concentration should be measured during critical moments of reproductive life in order to determine body condition and energy mobilization, due to their low or null correlations.

Ketosis is a major metabolic disorder that can lead to huge economic losses in postpartum dairy cows by influencing milk production and reproduction performance. Therefore, it is very important to understand the characteristics and significance of plasma GH levels and dynamic changes in postpartum dairy cows for finding pathogenesis of subclinical ketosis (SK). The present study aimed to determine the role of growth hormone (GH) from the onset of SK to the fifth week postpartum and to explain the variations in GH, and metabolic markers namely, β-hydroxybutyric acid (BHBA), non-esterified fatty acid (NEFA) and glucose (GLU) at early and later SK stages in postpartum Holstein cows. A 5-wk test and an intraday 12-h test were conducted in postpartum Holstein cows. Both tests were carried out every three hours from 10:00–22:00 for 7–14 days postpartum (12-h test: n = 16) to determine plasma concentrations of GH, BHBA, NEFA and GLU. The 5-wk test results showed that GH, BHBA and NEFA concentrations were significantly higher in the SK group during the five-weeks postpartum (p < 0.01); GLU concentration was significantly lower in the SK group (p < 0.01). Intraday 12-h test results revealed that the feeding time affected the plasma concentrations of GH, BHBA, NEFA and GLU. After 1-h of feeding time, GH concentrations decreased, while BHBA, NEFA and GLU concentrations increased. After 4-h of feeding time GH, BHBA and NEFA had the highest plasma concentrations, and GLU the lowest. In both experiments, GH was positively correlated with BHBA, NEFA, and negatively correlated with GLU. It can be suggested that GH has a potential role in development and aetiology of subclinical ketosis. [ABSTRACT FROM AUTHOR]

Simple Summary: This work aims to address the use of biomarkers that can provide us with information on the previous nutrition levels of wild rabbits, a keystone species that has drastically reduced in the last few years. Non-esterified fatty acids (NEFA), plasmatic urea nitrogen (PUN), albumin, glutamate and total protein metabolites were analysed. Additionally, we examined the potential of these metabolites as biomarkers for the nutritional and conservation status of European rabbits to further the biological knowledge of this species and contribute to its conservation. European wild rabbit (Oryctolagus cuniculus) populations have drastically reduced, and recently, rabbits have been classed as "endangered" by the IUCN. This animal plays an important ecological role in Mediterranean ecosystems and its introduction could significantly contribute to ecological restoration. Rabbits have high nutrient requirements that apparently cannot be covered in all ecosystems, and there are clues that nutrition can limit their abundance and density. On the other hand, some studies reflect the effects of food availability on the metabolomic status of other animal species, but there are no specific studies on this keystone species. The main aim of this work is to find biomarkers to assess the previous levels of ingestion of European rabbits (Oryctolagus cuniculus). To address this gap, gastric content and blood samples were collected from European rabbits (n = 99) in a Mediterranean area for the analysis of glucose, non-esterified fatty acids (NEFA), plasmatic urea nitrogen (PUN), albumin, glutamate and total protein metabolites. Depending on their previous feed intake (gastric content and the ratio between the gastric content and the weight of the animal), the animals were divided into two groups (lower and normal previous feed intake). Our work shows that the metabolomic profiles of the animals were affected. Levels of glucose (+82%; p = 0.0003), NEFA (−61%; p = 0.0040) and PUN (+139%; p < 0.001) were different in the animals with lower previous feed intake than the animals with normal previous feed intake. This work summarises that metabolic phenotype can be interesting when seeking to discover the limiting nutrients and food availability in diets that could affect the ecological fitness and conservation of European wild rabbits. It is important to mention that in this work, only the effects on six different metabolites have been analysed and more studies are necessary to complement the knowledge of possible metabolites that indicate the level of ingestion in this species and others. These (and new) biomarkers could be used as a tool to provide information about individual or population characteristics that other physiological parameters cannot detect, improving the conservation physiology field. [ABSTRACT FROM AUTHOR]

Background: The efect of genetic polymorphisms on fasting blood lipid levels have been widely studied but the efects of these within the context of a high-fat meal challenge remain less characterized. The current study aimed to investigate the association of SNPs in lipoprotein-related genes with blood lipid profles in healthy adults in the U.S. Methods: Subjects (n=393) between 18–66 years of age with BMIs ranging from 18.5–45 kg/m2 were enrolled the cross-sectional Nutritional Phenotyping Study. Among them, 349 subjects (men: 48%; women: 52%) gave consent for genotyping. SNPs in APOA5, APOB, APOC3, APOE, and LDLR were assessed. The association between lipid markers and genotypes was tested separately for each SNP with analysis of variance (ANOVA), adjusted for sex, age, and BMI. We also examined two-factor interactions between SNPs and sex, age, or BMI. Results: Women carrying the C allele of rs3135506 in APOA5 or men carrying the C allele of rs429358 in APOE had reduced HDL-cholesterol levels during fasting and postprandially. The C allele in APOE was also correlated to increased LDL-C levels. The TT genotype of rs2854116 in APOC3 was associated with elevated total cholesterol. Additive efect of the risk alleles of APOA5 and APOE or APOC3 and APOE was detected. Nevertheless, the tested SNPs had little impact on the postprandial triglyceride responses to the high-fat challenge meal. We found no signifcant efects of SNPs in APOB (rs1042034) or LDLR (rs2228671) on triglycerides, cholesterol, or free fatty acid levels. Conclusions: In healthy adults, fasting and postprandial cholesterol levels are strongly correlated with the tested APOA5, APOE, and APOC3 genotypes. Sex contributes to the genetic impact of the tested SNPs on lipid profles. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate which biochemical markers in the prepartum period of dairy cows influence the immediate postpartum period, the quality of colostrum, and the passive immunity transference in the calves. The experiment was performed on a commercial dairy farm with 52 pregnant multiparous Holstein cows. Animals that gave birth to twins or males were discarded from the experiment. On days -20 of the expected calving date and 24hours after calving, blood collections, body condition score assessments, and animals weighing were performed. Blood samples from calves were performed 24hours after colostrum intake. Calf plasma was used to estimate the passive immunity transfer by % brix and total plasma proteins (TPP). In the principal component analysis, it was shown that postpartum NEFA and BHBA was higher in cows with higher prepartum urinary pH and Ca lower prepartum. The cows with the highest NEFA and BHBA in pre and postpartum were the ones that had the lowest % brix in the colostrum. The % brix of the cow's colostrum directly influenced the % brix and TPP of the calves. The NEFA in the cows prepartum negatively influenced the markers of immunity, the higher the NEFA, the lower the % brix of the cows' colostrum, % brix of the calves, and TPP. In multivariate regression analyses it was shown that pre-calving NEFA was the marker that most influenced post-calving cow markers and calf % brix, along with colostrum time and % brix of the colostrum (P= 0.0092; r 2 = 0.83). Cows with higher values NEFA in the prepartum had lower calcemic in the immediate postpartum period. Prepartum NEFA was the marker that most influenced the cows' immediate postpartum period, being directly related to Ca serum, and also to the passive immunity transference., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6–8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables. [ABSTRACT FROM AUTHOR]

Leptin is involved in the modulation of insulin signaling in peripheral tissues, being closely associated with changes in lipid metabolism. This adipokine modifies inflammatory pathways that can interact with insulin targets in peripheral organs; however, the mechanisms remain unclear. Inflammatory and insulin signaling targets, cytokines, adiponectin, irisin and non-esterified fatty acid (NEFA) levels and enzymes of fatty acid anabolism were studied in the gastrocnemius of chronic centrally infused leptin (L), pair-fed and control rats. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) and c-Jun N-terminal kinase (JNK) was reduced in L rats (59% and 58%, respectively). The phosphorylation of the insulin receptor and Akt and adiponectin and irisin content was increased in L rats (154%, 157%, 308% and 329%, respectively). The levels of glucose-6-phosphate dehydrogenase, the mRNA content of acetyl Co-A carboxylase and NEFA concentrations were diminished in the muscles of L rats (59%, 50% and 61%, respectively). The activation of JNK correlated positively with STAT3 phosphorylation, tumoral necrosis factor-α and NEFA and negatively with irisin and Akt phosphorylation. These data suggest that the activation of insulin signaling targets and a decrease in NEFA content are associated with a reduction in muscle inflammation parameters, suggesting that leptin may integrate these pathways. [ABSTRACT FROM AUTHOR]

Keywords: haemolysis; icterus; NEFA; Siemens Atellica; stability EN haemolysis icterus NEFA Siemens Atellica stability e71 e73 3 04/25/23 20230515 NES 230515 To the Editor, Non-esterified fatty acids (NEFA) arise from the action of lipoprotein lipase (LPL) on triglycerides in adipose tissue. A NEFA/beta-hydroxybutyrate ratio greater than 2 suggests an underlying defect in beta oxidation of fatty acids, while a suppression of both NEFA and beta-hydroxybutyrate is indicative of hyperinsulinism [[2]]. [Extracted from the article]

The purpose of this study was to determine the link between insulin-like growth factor 1 (IGF-1), progesterone (PROG), non-esterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and glucose (GLU) and pregnancy probability after the first artificial insemination (AI) and during the first 100 days in milk (DIM), during the critical transition period. We determined levels of serum IGF-1, PROG, NEFA, BHB, and GLU in Holstein dairy cows via ELISA, using blood samples collected 7 days before parturition (DAP) until 21 days postparturition (DPP). The group was split into cows diagnosed pregnant at 100 DIM (PREG) and those that did not conceive at 100 and 150 DIM (NPREG). Serum IGF-1 and PROG median levels at 7 DAP were significantly higher in PREG vs. NPREG (p = 0.029), the only statistically significant differences across the subgroups. At 7 DAP, IGF-1 levels within the initial group showed a strong negative correlation with PROG (r = −0.693; p = 0.006), while for the PREG subgroup, the IGF-1 levels exhibited a very strong positive correlation with GLU (r = 0.860; p = 0.011) and NEFA (r = 0.872; p = 0.013). IGF-1 and PROG levels detected at 7 DAP may be useful to predict pregnancy at 100 DIM. The positive correlation of NEFA and GLU levels during the transition period demonstrates that the initial group is not in NEB; thus, the NEFA level was not a decisive factor for reproduction success.

Non-esterified fatty acids (NEFAs), key to energy metabolism, may become pathogenic at elevated levels, potentially eliciting immune reactions. Our laboratory's findings of reduced L-histidine in ketotic states, induced by heightened NEFA concentrations, suggest an interrelation with NEFA metabolism. This observation necessitates further investigation into the mitigating role of L-histidine on the deleterious effects of NEFAs. Our study unveiled that elevated NEFA concentrations hinder the proliferation of Bovine Mammary Epithelial Cells (BMECs) and provoke inflammation in a dose-responsive manner. Delving into L-histidine's influence on BMECs, RNA sequencing revealed 2124 genes differentially expressed between control and L-histidine-treated cells, with notable enrichment in pathways linked to proliferation and immunity, such as cell cycle and TNF signaling pathways. Further analysis showed that L-histidine treatment positively correlated with an increase in EdU-555-positive cell rate and significantly suppressed IL-6 and IL-8 levels (p < 0.05) compared to controls. Crucially, concurrent treatment with high NEFA and L-histidine normalized the number of EdU-555-positive cells and cytokine expression to control levels. Investigating the underlying mechanisms, Gab2 (Grb2-associated binder 2) emerged as a central player; L-histidine notably reduced Gab2 expression, while NEFA had the opposite effect (p < 0.05). Gab2 overexpression escalated nitric oxide (NO) production and IL6 and IL8 expression. However, L-histidine addition to Gab2 -overexpressing cells resulted in NO concentrations indistinguishable from controls. Our findings collectively indicate that L-histidine can counteract NEFA-induced inflammation in BMECs by inhibiting Gab2 expression, highlighting its therapeutic potential against NEFA-related metabolic disturbances. • L-histidine significantly mitigates inflammation in BMECs. • L-histidine modulates 2124 gene expressions in BMECs, notably affecting immunity and proliferation pathways. • L-histidine and high NEFA levels synergistically normalize cytokine expression and NO production in BMECs. • Gab2 emerges as a pivotal mediator in BMECs' inflammatory response. • L-histidine counteracts the pro-inflammatory effects of Gab2 overexpression in BMECs. [ABSTRACT FROM AUTHOR]

Simple Summary: Perinatal dairy cows face the challenge of maintaining the resilience of defense against invading pathogens. During the perinatal period, hormonal or metabolic changes cause the decline of immune function of dairy cows and further lead to varying degrees of immunosuppression. The results of this study indicate that, hormones, nonesterified fatty acids (NEFAs) and short-chain fatty acids (SCFAs) can regulate neutrophil migration and the NETs formation of dairy cows in vitro. These results help to further explain the effects of changes in hormone secretion and metabolites on immunosuppression and the increased risk of disease in perinatal dairy cows. Polymorphonuclear neutrophils (PMN) are the first line of defense against the invasion of foreign pathogenic microorganisms and play an essential role in the immune system of dairy cows. The changes in hormone secretion and metabolites of dairy cows during the perinatal period are the key factors that cause immunosuppression and increased risk of diseases. However, the effects of the hormone, nonesterified fatty acid (NEFA), and short-chain fatty acid (SCFA) on the transmammary epithelial migration of dairy cows and the formation of neutrophil extracellular traps (NETs) have rarely been studied. This study explored the effects of hormones, NEFAs and SCFAs on the neutrophil migration and NETs formation of dairy cows in vitro. It was found that P4 and Ac can regulate the transepithelial migration of PMN; SA and Pr can regulate the formation of NETs; E2, OA and Bt can regulate PMN transepithelial migration and NET formation. These results help to further explain the effects of changes in hormone secretion and metabolites on immunosuppression and the increased risk of disease in perinatal dairy cows. [ABSTRACT FROM AUTHOR]

In recent years, a wealth of factors are associated with increased risk of developing non-alcoholic fatty liver disease (NAFLD) and NAFLD is now thought to increase the risk of multiple extra-hepatic diseases. The aim of this review is first to focus on the role of ageing and sex as key, poorly understood risk factors in the development and progression of NAFLD. Secondly, we aim to discuss the roles of white adipose tissue (WAT) and intestinal dysfunction, as producers of extra-hepatic factors known to further contribute to the pathogenesis of NAFLD. Finally, we aim to summarise the role of NAFLD as a multi-system disease affecting other organ systems beyond the liver. Both increased age and male sex increase the risk of NAFLD and this may be partly driven by alterations in the distribution and function of WAT. Similarly, changes in gut microbiota composition and intestinal function with ageing and chronic overnutrition are likely to contribute to the development of NAFLD both directly (i.e. by affecting hepatic function) and indirectly via exacerbating WAT dysfunction. Consequently, the presence of NAFLD significantly increases the risk of various extra-hepatic diseases including CVD, type 2 diabetes mellitus, chronic kidney disease and certain extra-hepatic cancers. Thus changes in WAT and intestinal function with ageing and chronic overnutrition contribute to the development of NAFLD - a multi-system disease that subsequently contributes to the development of other chronic cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of different source of magnesium in prepartum diets on productive performance, blood metabolites, insulin resistance and health disorders in transition cows. Sixty cows from 21 days prepartum were randomly assigned to 4 experimental treatments. Treatments were control treatment (Mg at NRC recommendation), magnesium sulfate treatment, magnesium carbonate treatment and magnesium oxide treatment (Mg was 0.60% of ration DM). Experimental diets increased DM and NDF digestibility (P<0.05). However, Calf and placenta weight, body weight changes and BCS were not affected by treatments. The incidence of retained placenta and hypomagnesemia decreased in experimental treatments (P<0.05). Magnesium oxide and carbonate treatments tended to increase milk yield (P=0.08). Milk fat increased in the control diet (P<0.05). Experimental diets decreased plasma NEFA and cholesterol and improved plasma Mg and Ca (P<0.05). Control treatment had the lowest rate of glucose CR (%) and RQUICKI (P<0.05). [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Systematic studies on the phenotypic consequences of variants causal of HNF1A-MODY are rare. Our aim was to assess the phenotype of carriers of a single HNF1A variant and genetic and clinical factors affecting the clinical spectrum. Methods: We conducted a family-based multigenerational study by comparing heterozygous carriers of the HNF1A p.(Gly292fs) variant with the non-carrier relatives irrespective of diabetes status. During more than two decades, 145 carriers and 131 non-carriers from 12 families participated in the study, and 208 underwent an OGTT at least once. We assessed the polygenic risk score for type 2 diabetes, age at onset of diabetes and measures of body composition, as well as plasma glucose, serum insulin, proinsulin, C-peptide, glucagon and NEFA response during the OGTT. Results: Half of the carriers remained free of diabetes at 23 years, one-third at 33 years and 13% even at 50 years. The median age at diagnosis was 21 years (IQR 17–35). We could not identify clinical factors affecting the age at conversion; sex, BMI, insulin sensitivity or parental carrier status had no significant effect. However, for 1 SD unit increase of a polygenic risk score for type 2 diabetes, the predicted age at diagnosis decreased by 3.2 years. During the OGTT, the carriers had higher levels of plasma glucose and lower levels of serum insulin and C-peptide than the non-carriers. The carriers were also leaner than the non-carriers (by 5.0 kg, p=0.012, and by 2.1 kg/m2 units of BMI, p=2.2 × 10−4, using the first adult measurements) and, possibly as a result of insulin deficiency, demonstrated higher lipolytic activity (with medians of NEFA at fasting 621 vs 441 μmol/l, p=0.0039; at 120 min during an OGTT 117 vs 64 μmol/l, p=3.1 × 10−5). Conclusions/interpretation: The most common causal variant of HNF1A-MODY, p.(Gly292fs), presents not only with hyperglycaemia and insulin deficiency, but also with increased lipolysis and markedly lower adult BMI. Serum insulin was more discriminative than C-peptide between carriers and non-carriers. A considerable proportion of carriers develop diabetes after young adulthood. Even among individuals with a monogenic form of diabetes, polygenic risk of diabetes modifies the age at onset of diabetes. [ABSTRACT FROM AUTHOR]

Non-esterified fatty acids (NEFAs) and Insulin-like growth factor-I (IGF-1) concentrations are modified after the induction of a "male effect". The present study examined the effect of the introduction of males into a group of females that were previously isolated from males, during different phases of the sexual cycle, to determine the changes to the NEFAs and IGF-1 concentrations. Sixty-four does were divided into six groups. The males were introduced with the females at different points after sponge removal. Introduction was carried out 48 h (n = 10, Group 48H), 72 h (n = 12, Group 72H), 4 days (n = 10, Group 4 D), 13 days (n = 10, Group 13 D) or 18 days after sponge removal (n = 10, Group 18 D), and a control group was implemented that had no contact with males (n = 12, Control Group). Plasma samples were taken every day to determine daily progesterone (P4) and NEFAs concentrations, and every second day for IGF-1 determination. No effects from the experimental groups were observed on the mean NEFAs or IGF-1 concentrations (p > .05). No differences between the time before male introduction and after male introduction were observed on the NEFAs concentrations (p > .05) or IGF-1 concentrations (p > .05). On the whole, only differences were observed in the NEFAs concentrations between the follicular and the luteal phases (9.48 ± 0.38 vs 8.15 ± 0.15 mg/dL for follicular and luteal phases, respectively, p

This study aimed to investigate the effect of vitamin D administered 24 h after calving of dairy cows on calcium-phosphorus metabolism, carbohydrate, lipid and liver metabolism, and inflammatory response. Twenty multiparous Holstein cows were randomly assigned to the experimental (EG) and control group (CG). The EG received 5,000,000 IU vitamin D3 (5 mL) 24 h after parturition intramuscularly, whereas the CG group received 5 mL of 0.9% NaCl. Blood samples were taken 24 h after parturition before treatments and at the 3rd, 7th, 14th, and 28th days of lactation. Serum NEFA, BHBA, haptoglobin, serum amyloid A (SAA), ceruloplasmin, calcium, phosphorus, parathormone, total protein, triglyceride, AST, and GGT were measured. In addition, total bilirubin, albumin, total cholesterol, and vitamin A concentrations were also measured to calculate liver activity index and the liver functionality index. Subclinical hypocalcemia (SCH) was observed in only one cow in the EG and five in the CG after the 3rd day postpartum. NEFA levels in the EG significantly differed on days 7, 14, and 28 when compared to vitamin D pretreatment values. However, NEFA levels in the CG differed only between day 28 postpartum and the 1st day (p < 0.05). Negative correlation was determined between vitamin D and NEFA (p < 0.01). Conversely, negative correlations were observed between calcium and NEFA, haptoglobin, SAA (p < 0.05). In conclusion, it can be suggested that vitamin D administration can prevent SCH after the 3rd day and has limited positive effects on postpartum NEFA levels. [ABSTRACT FROM AUTHOR]

ABSTRACT This study aimed to evaluate the effects of different nutritional plans on the productive, physiological and metabolic parameters of F1 ½ Holstein x ½ Zebu cows in different stages of lactation. Sixty lactating cows were allotted to a completely randomized 5 x 3 factorial design with five feed allowances and three lactation periods. The dry matter intake, milk yield and heart rate were reduced by 5.69kg, 2.41kg and 10.36 beats/min (morning) and 10.25 beats/min (afternoon) for each 1% feed restriction, respectively. There was no difference in the concentration of glucose, total protein, albumin, cholesterol and non-esterified fatty acids for cows subjected to different feed allowances, with means of 95.25, 7.98, 2.95, 121.68 and 0.45mg/dL, respectively. Feed restriction of up to 2.50% BW is a cost reduction strategy that does not alter milk yield, regardless of the stage of lactation.

Abstract Background The objective of this study was to investigate the metabolic and osmotic effects of different doses of glycerol or a glycerol – propylene glycol mixture in Sarda sheep with the aim to identify those able to beneficially modify ewe’s metabolic status without harmful changes in red blood cell (RBC) indices. Thereafter, the selected doses were tested for their effects on ewe’s ovarian activity during an induced follicular phase and compared to the effects of a hormonal treatment with equine chorionic gonadotrophin (eCG). Results Glycerol was administered alone (G groups: 90% glycerol and 10% water; % v/v) or in combination with propylene glycol (M groups: 70% glycerol, 20% propylene glycol, 10% water; % v/v). Treatments were formulated to provide 100, 75, 50 and 25% of the amount of energy supplied in previous experiments. Obtained results showed that the formulations G75 and M75 (22.5 and 18.2% on DM basis, respectively) induce metabolic changes comparable to those induced by M100. The latter dose has been already evaluated for its effects on sheep metabolism and reproductive performance. However, with these high doses, plasma osmolality increased significantly, and RBC indices showed significant alterations. The low dose groups (G25 and M25, 8.6 and 6.9% on DM basis, respectively) did not show any alterations in plasma osmolality and RBC indices, but the metabolic milieu differed markedly from that of M100. Between the medium dose groups, M50 (12.9% on DM basis) showed a more comparable milieu to M100 than G50 (15.9% on DM basis) and no RBC alterations. Therefore, M75, G75 and M50 doses were tested for their effect on ovarian functions and proved to be equally effective as eCG. Conclusion The results of the present study evidenced an alteration of RBC indices, and possibly of their functions, as a side effect of glycerol administration at high doses in the diet of ewes. Therefore, protocols foreseeing the administration of glycerol should be tested for their effects on RBC indices and functions. In general terms, the medium dose of the glucogenic mixture (12.9% of dietary DM on offer) should be preferred.

The aim was to evaluate if 1-2 propanodiol plus calcium propionate (glycogenic precursor) supplementation during the transition period in high yielding dairy cows reduces metabolic and reproductive dysfunctions during early lactation. Cows (n= 202) were divided into two homogeneous groups regarding number of lactations and body condition score. 1) Treated group (GG; n= 112) received 60 g/cow/dfor15 d of a glycogenic precursor during the transition period. 2) Control group (GC; n= 90) received no treatment. Postpartum levels of beta hydroxybutyrate (BHB) (GG= 0.9 ± 0.2 mmol/L vs GC =1.3 ± 0.2 mmol/L; P