Intracellular Ca2+ signaling and ORAI calcium release-activated calcium modulator 1 (ORAI1) are associated with hepatic lipidosis in dairy cattle

2021 ◽  
Author(s):  
Ming Li ◽  
Wei Yang ◽  
Jianan Wen ◽  
Juan J Loor ◽  
Ahmad Aboragah ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Liver ◽  
Er Stress ◽  
Dairy Cows ◽  
Calcium Release ◽  
Acid Synthesis ◽  
Isolated Hepatocytes ◽  
Control Group ◽  
Hepatic Lipidosis

Abstract Fatty liver is a common metabolic disorder afflicting dairy cows during the periparturient period and is closely associated with endoplasmic reticulum (ER) stress. The onset of ER stress in humans and mice alters hepatic lipid metabolism, but it is unknown if such event contributes to fatty liver in dairy cows soon after parturition. ORAI1 is a key component of the store-operated Ca2+ entry mechanism regulating cellular Ca2+ balance. The purpose of this study was to investigate the role of ORAI1 on hepatic lipidosis via ER stress in dairy cows. Liver tissue biopsies were collected from Holstein cows diagnosed as healthy (n=6) or with hepatic lipidosis (n=6). Protein and mRNA abundance of ER stress-related targets, lipogenic targets or the transcription regulator SREBP1 and ORAI1 were greater in cows with lipidosis. In vitro, hepatocytes were isolated from four healthy female calves and used for culture with a 1.2 mM mixture of fatty acids (oleic, linoleic, palmitic, stearic, and palmitoleic acid) for various times (0, 3, 6, 9 or 12 h). As incubation time progressed, increases in concentration of Ca2+ and abundance of protein kinase RNA-like ER kinase (PERK), inositol requiring protein-1α (IRE1α), and activating transcription factor-6 (ATF6) protein in response to exogenous fatty acids underscored a mechanistic link among Ca2+, fatty acids and ER stress. In a subsequent study, hepatocytes were transfected with small interfering RNA (siORAI1) or the ORAI1 inhibitor BTP2 for 48 h or 2 h followed by a challenge with the 1.2 mM mixture of fatty acids for 6 h. Compared with control group, silencing or inhibition of ORAI1 led to decreased abundance of fatty acid synthesis (FASN, SREBP1 and ACACA) and ER stress-related proteins in bovine hepatocytes. Overall, data suggested that NEFA through ORAI1 regulate intracellular Ca2+ signaling, induce ER stress, and lead to lipidosis in isolated hepatocytes.

Evaluation of fructosamine as a new biomarker for diagnosis of hepatic lipidosis in dairy cows

2015 ◽  
Vol 55 (8) ◽  
pp. 1005 ◽  
Author(s):  
Masoud Mostafavi ◽  
Hesam A. Seifi ◽  
Mehrdad Mohri ◽  
Abdullah Jamshidi
Keyword(s):  
Fatty Acids ◽  
Fatty Liver ◽  
Dairy Cows ◽  
Likelihood Ratio ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Serum Total Bilirubin ◽  
Hepatic Lipidosis ◽  
Esterified Fatty Acids ◽  
Serum Fructosamine

An abattoir-based cohort study using liver and serum specimens from Holstein dairy cows (452 healthy and 54 fatty liver cases) was conducted. Serum fructosamine and other biochemical parameters and fat content of liver specimens were measured. There were significant negative correlations of fructosamine with hepatic lipid content (P = 0.001), and serum total bilirubin (P = 003) and significant positive correlation with glucose (P < 0.02), albumin (P < 0.0001) and cholesterol (P < 0.0001) within normal cows. In fatty liver-affected cows significant positive correlations were seen between fructosamine and cholesterol (P < 0.0001) and albumin (P < 0.0001). In addition fructosamine had a significant negative correlation with the ratio of non-esterified fatty acids to cholesterol in both normal (P < 0.0001) and fatty liver-affected cows (P = 0.006). We found that serum fructosamine concentration was lower (P < 0.001) in cows suffering from fatty liver. The area under the receiver operating characteristic curve of fructosamine for diagnosis of fatty liver was 67.6. Optimum fructosamine cut-point based on the maximum total of sensitivity (SE) and specificity (SP) was <213 µmol/L (SE = 71%; SP = 65). Cows with serum fructosamine concentrations below 213 µmol/L were 4.5 times more likely to have hepatic lipidosis (odds ratio = 4.5; 95% CI = 2.4–8.6; P < 0.0001). We found that fructosamine showed a combination of high SE, SP, which was greater than aspartate aminotransferase, non-esterified fatty acids, β-hydroxybutyrate, total cholesterol, bile acids and bilirubin. In addition, fructosamine showed a positive likelihood ratio of 2.0, and negative likelihood ratio of 0.45. In conclusion, the present results indicate that fructosamine measurement could improve the diagnosis of fatty liver in dairy cows.

scholarly journals Sirtuin 3 Restores Synthesis and Secretion of Very Low-Density Lipoproteins in Cow Hepatocytes Challenged with Nonesterified Fatty Acids In Vitro

2021 ◽  
Vol 8 (7) ◽  
pp. 121
Author(s):  
Dongmei Xing ◽  
Baogen Wang ◽  
Hong Lu ◽  
Tao Peng ◽  
Jianming Su ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Dairy Cows ◽  
Low Density Lipoproteins ◽  
Mrna Abundance ◽  
Low Density ◽  
Sirtuin 3 ◽  
Very Low Density Lipoproteins ◽  
Nonesterified Fatty Acids ◽  
Tag Accumulation

Fatty liver is closely associated with elevated concentrations of nonesterified fatty acids (NEFA) and a low level of very low-density lipoproteins (VLDL) in blood of dairy cows. High NEFA inhibit the VLDL synthesis and assembly, and cause hepatic triacylglycerol (TAG) deposition. Sirtuin 3 (SIRT3), a mitochondrial deacetylase, antagonizes NEFA-induced TAG accumulation through modulating expressions of fatty acid synthesis and oxidation genes in cow hepatocytes. However, the role of SIRT3 in the VLDL synthesis and assembly was largely unknown. Here we aimed to test whether SIRT3 would recover the synthesis and assembly of VLDL in cow hepatocytes induced by high NEFA. Primary cow hepatocytes were isolated from 3 Holstein cows. Hepatocytes were infected with SIRT3 overexpression adenovirus (Ad-SIRT3), SIRT3-short interfering (si) RNA, or first infected with Ad-SIRT3 and then incubated with 1.0 mM NEFA (Ad-SIRT3 + NEFA). Expressions of key genes in VLDL synthesis and the VLDL contents in cell culture supernatants were measured. SIRT3 overexpression significantly increased the mRNA abundance of microsomal triglyceride transfer protein (MTP), apolipoprotein B100 (ApoB100) and ApoE (p < 0.01), and raised VLDL contents in the supernatants (p < 0.01). However, SIRT3 silencing displayed a reverse effect in comparison to SIRT3 overexpression. Compared with NEFA treatment alone, the Ad-SIRT3 + NEFA significantly upregulated the mRNA abundance of MTP, ApoB100 and ApoE (p < 0.01), and increased VLDL contents in the supernatants (p < 0.01). Our data demonstrated that SIRT3 restored the synthesis and assembly of VLDL in cow hepatocytes challenged with NEFA, providing an in vitro basis for further investigations testing its feasibility against hepatic TAG accumulation in dairy cows during the perinatal period.

scholarly journals Daytime Grazing in Mountainous Areas Increases Unsaturated Fatty Acids and Decreases Cortisol in the Milk of Holstein Dairy Cows

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3122
Author(s):  
Jalil Ghassemi Nejad ◽  
Bae-Hun Lee ◽  
Ji-Yung Kim ◽  
Kyung-Il Sung ◽  
Hong-Gu Lee
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Dairy Cows ◽  
Milk Fat ◽  
Unsaturated Fatty Acids ◽  
Control Group ◽  
Milk Fatty Acid ◽  
Omega 3 ◽  
Mountainous Areas ◽  
Lactating Cows

The effects of grazing lactating cows in mountainous areas for 12 and 24 h compared with the confined indoor system were evaluated by examining the overall milk fatty acid and cortisol. Twenty-one dairy cows were allocated to three treatment groups: (1) control (confined management system in a free-stall barn; TMR based), (2) grazing for 12 h (12hG; TMR plus grazing pasture), and (3) grazing for 24 h (24hG; pasture-based feeding system). Dry matter intake was higher in the control and 12hG groups than in the 24hG group. The yields of total milk and the 3.5% fat-corrected milk were the lowest in the 24hG group. Milk fat was the highest in the 24hG group and higher in 12hG compared with the control group. Milk protein and lactose levels were the highest in the 12hG group. The highest somatic cell count was observed in the 24hG group. The saturated fatty acid levels were higher in the control group compared with the 12hG and 24hG groups. There was no difference in overall mono-unsaturated fatty acids between 12hG and 24hG groups. Poly-unsaturated fatty acids were higher in the 12hG group compared with the control and 24hG groups. There was no difference in omega-6 (ω-6) fatty acids among the groups, and omega-3 fatty acids were higher in the 12hG group than in the control group. Milk cortisol was the highest in the 24hG group and higher in the control group compared with the 12hG group. Taken together, grazing for 12 h is advisable for farms that have access to mountainous areas to improve the milk fatty acid profile and decrease the stress levels in high-yielding Holstein lactating cows.

Effect of chronic ingestion of ethanol on in vitro uptake of lipids and glucose in the rabbit jejunum

1984 ◽  
Vol 246 (2) ◽  
pp. G120-G129
Author(s):  
A. B. Thomson
Keyword(s):  
Fatty Acids ◽  
Food Intake ◽  
Weight Control ◽  
Bulk Phase ◽  
Unstirred Layer ◽  
Control Group ◽  
Cholesterol Uptake ◽  
Incremental Change ◽  
Rabbit Jejunum

This study was undertaken to determine the effect of chronic feeding of ethanol on the in vitro jejunal uptake of lipids and glucose. The first group of rabbits was fed ad libitum (CAL); the food intake of a second control group [weight control (WC)] was restricted to match their gain in body weight with that of a chronically ethanol-fed group (ETH); and the food intake of a third control group [food control (FC)] was restricted to match the food intake with that of ETH. There was a marked decline in cholesterol uptake in WC and FC compared with CAL, and cholesterol uptake in ETH was intermediate between the higher value in CAL and the lower value in WC and FC. The uptake of fatty acids 4:0-12:0 was similar in the CAL, FC, WC, and ETH groups, both when the bulk phase was stirred and unstirred; the uptake of fatty acids 16:0 and 18:0 was lower in WC and FC than in CAL; and the uptake of fatty acids 14:0, 16:0, and 18:0 was even lower in ETH. The uptake of a homologous series of fatty alcohols was greater in WC and ETH than in CAL at five different rates of stirring of the bulk phase. When the uptake of fatty acids 6:0-12:0 was corrected for unstirred layer resistance, a linear relation was noted between fatty acid chain length and the natural logarithm of rate of uptake/aqueous diffusion coefficient, and the steeper slope in WC and ETH than in CAL represented a higher incremental change in free energy. Glucose uptake was similar in CAL, WC, and FC but was greater in ETH from 5 to 40 mM glucose. These studies demonstrate that 1) weight restriction, food restriction, and chronic ethanol feeding are associated with a change in the effective resistance of the unstirred layer and in the passive permeability properties of the rabbit jejunum, and 2) ethanol has a differential effect on passive permeation of short-, medium-, and long-chain fatty acids and cholesterol.

357 CALCIUM RELEASE INDUCED BY THIMEROSAL AND INOSITOL 1,4,5-TRIPHOSPHATE IN HEAT-SHOCKED PORCINE OOCYTES

2007 ◽  
Vol 19 (1) ◽  
pp. 294
Author(s):  
J.-K. Tseng ◽  
P.-C. Tang ◽  
J.-C. Ju
Keyword(s):  
Heat Shock ◽  
Calcium Release ◽  
Prolonged Exposure ◽  
Imaging System ◽  
Developmental Competence ◽  
Control Group ◽  
Acetoxymethyl Ester ◽  
Treatment Groups ◽  
All Treatment

Elevated ambient temperature has been known to be deleterious to the developmental competence of mammalian oocytes and embryos, although the mechanism is still unclear. The objective of this study was to determine the effect of heat shock (HS) on the alteration of intracellular calcium concentrations ([Ca2+]i) of matured pig oocytes by two different calcium releasing agents. Porcine cumulus–oocyte complexes were aspirated from the follicles (3–6 mm) and subjected to standard in vitro maturation procedure for 42 h. Matured oocytes were then randomly allocated to different heat treatments at 41.5°C for 0 (Control, C0h), 1 (HS1h), 2 (HS2h), or 4 h (HS4h). An additional control group was cultured for 4 h without heat shock (C4h). Oocytes were incubated with 2 µM fura-2 acetoxymethyl ester (AM) and 0.02% pluronic F-127 in Ca2+-free PBS (40 min) following heat shock, and then washed with Ca2+-free PBS (30 min) for detection of [Ca2+]i. Fluorescent images were captured with alternative excitation wavelengths at 340/380 nm by a rotating chopper disk equipped with an Axon imaging system. Data from both experiments were analyzed by ANOVA using the General Linear Model (GLM) of the SAS (SAS Institute, Inc., Cary, NC, USA). In Experiment 1, matured oocytes were activated by 200 mM thimerosal (10 min) following heat treatment. The maximal [Ca2+]i in the HS2h group was the highest among all treatment groups. The lowest maximal peak of [Ca2+]i was observed in the HS4h group, but it was still higher than that in the C4h group (P < 0.05). The total amount of Ca2+ release represented by the total area of the peaks in C4h was lower than in any other groups except HS4h (P < 0.05). In Experiment 2, each matured oocyte was injected with approximately 10 pL of inositol 1,4,5-triphosphate (IP3, 0.5 mM); the Ca2+ transient was recorded as described in the previous experiment. The maximal value of [Ca2+]i in the C4h group was still the lowest among the heat-shocked and C0h groups (P < 0.05). The total Ca2+ release in the HS2h group was the highest among all treatment groups, but only significantly higher than the HS1h and C4h groups (P < 0.05). A similar pattern of Ca2+ release in HS-oocytes was induced by thimerosal and IP3 stimulations. These results indicate that Ca2+ releasing capacity of matured pig oocytes is enhanced by a shorter duration of heat shock, but declines after prolonged exposure of heat shock and/or in vitro culture. The differential Ca2+ releasing capacity of heat-shocked oocytes prior to fertilization revealed physiological changes of pig oocytes after heat shock. This finding provides further insight for the low fertilization and developmental competence that occurs in farm species during hot seasons.

Relationship between fish oil intake by dairy cows and the yield of eicosapentaenoic acid and docosahexaenoic acid in their milk

2001 ◽  
Vol 2001 ◽  
pp. 199-199 ◽  
Author(s):  
C. Rymer ◽  
C. Dyer ◽  
D.I. Givens ◽  
R. Allison
Keyword(s):  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Fish Oil ◽  
Dairy Cows ◽  
Fish Consumption ◽  
Essential Fatty Acids ◽  
Epa And Dha ◽  
The Uk

The dietary essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are predominantly found in fish oil, but fish consumption in the UK is low. Increasing the yield of EPA and DHA in cows’ milk would increase human intakes of EPA and DHA, and this can be achieved by including fish oil in cows’ diets. However, because EPA and DHA are susceptible to rumen biohydrogenation, their transfer efficiency into milk is low.In vitroobservations by Gulatiet al. (1999) suggested that if the concentration of fish oil in the rumen exceeded 1 mg/ml, EPA and DHA were not hydrogenated. The objectives of this study were therefore to determine the relationships between fish oil intake by dairy cows, and the probable concentrations of fish oil in the cows’ rumen, with the yield of EPA and DHA in their milk.

On the Specificity of the Herbicide Chlorsulfuron in Intact Spinach Chloroplasts

1985 ◽  
Vol 40 (11-12) ◽  
pp. 917-918 ◽  
Author(s):  
Uwe Homeyer ◽  
D. Schulze-Siebert ◽  
G. Schultz
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Acid Synthesis ◽  
Spinach Chloroplasts ◽  
Transamination Reaction ◽  
Dehydrogenase Complex

Abstract In vitro incubation of intact spinach chloroplasts with 1 mᴍ Pyruvate was used to study the specificity of action of the herbicide Chlorsulfuron on the synthesis of valine, alanine and fatty acids. As a result, increasing concentrations of the herbicide strongly inhibited valine synthesis while fatty acid synthesis via pyruvate dehydrogenase complex (PDC) and alanine formation by transamination reaction was promoted.

scholarly journals Fatty Acid Synthesis Is Essential for Survival of Cryptococcus neoformans and a Potential Fungicidal Target

2007 ◽  
Vol 51 (10) ◽  
pp. 3537-3545 ◽  
Author(s):  
Methee Chayakulkeeree ◽  
Thomas H. Rude ◽  
Dena L. Toffaletti ◽  
John R. Perfect
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cryptococcus Neoformans ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Yeast Cells ◽  
Synthase Inhibitor ◽  
The Brain

ABSTRACT Fatty acid synthase in the yeast Cryptococcus neoformans is composed of two subunits encoded by FAS1 and FAS2 genes. We inserted a copper-regulated promoter (P CTR4-2 ) to regulate FAS1 and FAS2 expression in Cryptococcus neoformans (strains P CTR4-2 /FAS1 and P CTR4-2 /FAS2, respectively). Both mutants showed growth rates similar to those of the wild type in a low-copper medium in which FAS1 and FAS2 were expressed, but even in the presence of exogenous fatty acids, strains were suppressed in growth under high-copper conditions. The treatment of C. neoformans with fluconazole was shown to have an increased inhibitory activity and even became fungicidal when either FAS1 or FAS2 expression was suppressed. Furthermore, a subinhibitory dose of fluconazole showed anticryptococcal activity in vitro in the presence of cerulenin, a fatty acid synthase inhibitor. In a murine model of pulmonary cryptococcosis, a tissue census of yeast cells in P CTR4-2 /FAS2 strain at day 7 of infection was significantly lower than that in mice treated with tetrathiomolybdate, a copper chelator (P < 0.05), and a yeast census of P CTR4-2 /FAS1 strain at day 14 of infection in the brain was lower in the presence of more copper. In fact, no positive cultures from the brain were detected in mice (with or without tetrathiomolybdate treatment) infected with the P CTR4-2 /FAS2 strain, which implies that this mutant did not reach the brain in mice. We conclude that both FAS1 and FAS2 in C. neoformans are essential for in vitro and in vivo growth in conditions with and without exogenous fatty acids and that FAS1 and FAS2 can potentially be fungicidal targets for C. neoformans with a potential for synergistic behavior with azoles.

Effects of calcium salts of medium-chain fatty acids on plasma metabolite and hormone concentrations in early lactating dairy cows

2014 ◽  
Vol 54 (10) ◽  
pp. 1699
Author(s):  
T. Sugino ◽  
A. Tateno ◽  
G. Ueno ◽  
K. Kawashima ◽  
T. Okimura ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Dairy Cows ◽  
Control Group ◽  
Calcium Salts ◽  
Treatment Groups ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Lactating Dairy Cows ◽  
Plasma Metabolite ◽  
Chain Fatty Acids

To elucidate the effects of medium-chain fatty acids (MCFA) on milk production and plasma metabolite and hormone concentrations in early lactating dairy cows, 10 multiparous Holstein dairy cows were randomly assigned to two dietary treatment groups after parturition. One group was fed a diet supplemented with calcium salts of MCFA (MCFA-Ca) for 8 weeks after parturition, while the other group was fed the same diet without the supplement (control). MCFA-Ca, containing 60% caprylic acid and 40% capric acid, was added to a total mixed ration (TMR) at 1.5% of the dietary dry matter (DM). Cows were offered the TMR ad libitum. DM intake, daily gain in bodyweight, milk yield, milk fat content and milk protein content did not differ between the two treatment groups. The MCFA-Ca diet decreased plasma glucose and triglyceride concentrations (P < 0.05), while plasma concentrations of total and free cholesterols tended to increase (P < 0.10). Plasma ghrelin was maintained at a higher concentration (P < 0.05) in cows fed the MCFA-Ca diet than in the control group. Relative to the control diet, the MCFA-Ca diet decreased plasma insulin concentration (P < 0.05) and numerically increased plasma glucagon concentration, resulting in a lower insulin : glucagon ratio (P < 0.05). In conclusion, plasma metabolite and hormone concentrations were affected by the MCFA-Ca diet, suggesting that MCFA-Ca supplementation may change endocrine functions and nutrient metabolism in early lactating cows, ultimately resulting in an enhanced catabolic state.

Control of Fatty Acid Synthesis in White Adipose Tissue by Insulin: Coordination Between the Mitochondrial Citrate Transporter and Pyruvate Dehydrogenase

1974 ◽  
Vol 52 (10) ◽  
pp. 813-821 ◽  
Author(s):  
Carol M. Schiller ◽  
Wayne M. Taylor ◽  
Mitchell L. Halperin
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Active Form ◽  
Acid Synthesis ◽  
Citrate Transporter ◽  
Maximal Activation ◽  
Initial Decrease ◽  
Preincubation Medium

The transport of citrate out of adipose tissue mitochondria is inhibited by palmitoyl-CoA. This inhibition varied inversely with the concentration of extramitochondrial exchanging anion.When adipose tissue is incubated in vitro, the rate of citrate output into the medium was increased by the addition of insulin. The tissue citrate content did not change significantly. Norepinephrine caused an initial decrease in the rate of citrate output (2.5 min). The tissue citrate content was approximately twofold higher at this time.When rats were fasted for 36 h, less than 40% of adipose tissue pyruvate dehydrogenase was in the active form. Optimal interconversion to the active form was achieved by preincubation with 4 mM Mg2+ in the absence of added Ca2+ (endogenous Ca2+ was approximately 25 μM). Citrate addition to the preincubation medium decreased this activation of pyruvate dehydrogenase. The inhibition induced by citrate correlated best with the concentration of 'free' citrate when the 'free' Mg2+ concentration was sufficient to cause near-maximal activation of pyruvate dehydrogenase.A hypothesis regarding the coordination of regulation of pyruvate conversion to fatty acids is formulated based on these findings.

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