scholarly journals NEFAs Influence the Inflammatory and Insulin Signaling Pathways Through TLR4 in Primary Calf Hepatocytes in vitro

2021 ◽  
Vol 8 ◽  
Author(s):  
Qinghua Deng ◽  
Liyin Du ◽  
Yuming Zhang ◽  
Guowen Liu

Transition dairy cows are often in a state of negative energy balance because of decreased dry matter intake and increased energy requirements, initiating lipid mobilization and leading to high serum β-hydroxybutyrate (BHBA) and non-esterified fatty acid (NEFAs) levels, which can induce ketosis and fatty liver in dairy cows. Inflammation and insulin resistance are also common diseases in the perinatal period of dairy cows. What is the relationship between negative energy balance, insulin resistance and inflammation in dairy cows? To study the role of non-esterified fatty acids in the nuclear factor kappa beta (NF-κB) inflammatory and insulin signaling pathways through Toll-like receptor 4 (TLR4), we cultured primary calf hepatocytes and added different concentrations of NEFAs to assess the mRNA and protein levels of inflammatory and insulin signaling pathways. Our experiments indicated that NEFAs could activate the NF-κB inflammatory signaling pathway and influence insulin resistance through TLR4. However, an inhibitor of TLR4 alleviated the inhibitory effects of NEFAs on the insulin pathway. In conclusion, all of these results indicate that high-dose NEFAs (2.4 mM) can activate the TLR4/NF-κB inflammatory signaling pathway and reduce the sensitivity of the insulin pathway through the TLR4/PI3K/AKT metabolic axis.

2021 ◽  
Author(s):  
Qinghua Deng ◽  
Liyin Du ◽  
Yuming Zhang ◽  
Guowen Liu

Abstract Dairy cows are often in a state of negative energy balance (NEB), because of decreased dry matter intake and increased energy requirements, initiating lipid mobilization and leading to high serum β-hydroxybutyrate and nonesterified fatty acid (NEFA) levels, which can induce ketosis and fatty liver in dairy cows. We all have known that inflammation and insulin resistance are also common diseases in perinatal period of dairy cows. So what is the relationship between negative energy balance, insulin resistance and inflammation in cow? In order to study the role of NEFAs in the NF-κB inflammatory and insulin signaling pathways through TLR4, we cultured bovine primary hepatocytes and added different concentrations of NEFAs to test the mRNA and protein levels of inflammatory and insulin signaling pathways. Our experiments indicated that NEFAs could activate the NF-κB inflammatory signaling pathway and influence insulin resistance through TLR4. However, an inhibitor of TLR4 alleviated the inhibitory effects of NEFAs on the insulin pathway. In conclusion, all of these results indicate that high-dose NEFAs can activate the TLR4/NF-κB inflammatory signaling pathway, and reduce the sensitivity of the insulin pathway through the TLR4/PI3K/AKT metabolic axis.


2021 ◽  
Author(s):  
Huijun Zhang ◽  
Xiang Gao ◽  
Kelei Li ◽  
Yandi Liu ◽  
Dhanushka S. Hettiarachichi ◽  
...  

Sandalwood seed oil improved insulin resistance by activating the PI3K/AKT insulin signaling pathway and by down-regulating the JNK/NF-κB inflammatory signaling pathway in the 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.


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.


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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