Elevated non-esterified fatty acids impair survival and promote lipid accumulation and pro-inflammatory cytokine production in bovine endometrial epithelial cells

2018 ◽  
Vol 30 (12) ◽  
pp. 1770 ◽  
Author(s):  
W. Chankeaw ◽  
Y. Z. Guo ◽  
R. Båge ◽  
A. Svensson ◽  
G. Andersson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Cell Viability ◽  
Lipid Accumulation ◽  
Negative Effects ◽  
Inflammatory Cytokine Production ◽  
Esterified Fatty Acids ◽  
Proliferation And Apoptosis ◽  
High Concentrations ◽  
Endometrial Epithelial Cells

Elevated non-esterified fatty acids (NEFAs) are associated with negative effects on bovine theca, granulosa and oviductal cells but the effects of NEFAs on bovine endometrial epithelial cells (bEECs) are not as well documented. The objective of this study was to define the effects of NEFAs on bEECs. Postprimary bEECs were treated with 150, 300 or 500 µM of either palmitic acid (PA), stearic acid (SA) or oleic acid (OA) or a mixture of NEFAs (150 µM of each FA) or 0.5% final concentration of vehicle ethanol (control). Viability and proliferation of bEECs exposed to 150 µM of each NEFA or a mixture of NEFAs were unaffected. Increased lipid accumulation was found in all treated groups (P < 0.01). In cells exposed to 500 µM of each NEFA and 300 µM PA decreased cell viability (P < 0.001), proliferation (P < 0.05) and increased apoptosis (P < 0.05) were observed. Treatment with 500 µM OA, PA and SA had the strongest effects on cell viability, proliferation and apoptosis (P < 0.05). Treatment with PA and OA increased interleukin-6 (IL-6) concentrations (P < 0.05), whereas only the highest concentration of PA, OA and SA stimulated IL-8 production (P < 0.05). These results suggest that high concentrations of NEFAs may impair endometrial function with more or less pronounced effects depending on the type of NEFA and time of exposure.

scholarly journals The Effects of Short Chain Fatty Acids (Butyrate) on the Permeability, Cell Viability, and Inflammatory Changes Due to Oxidative Stress in Lung Epithelial Cells

2019 ◽  
Vol 20 (-1) ◽  
pp. 37-37
Author(s):  
Abdullah Burak Yildiz ◽  
◽  
Nur Konyalilar ◽  
Duygu Yazici ◽  
Hasan Bayram ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Epithelial Cells ◽  
Cell Viability ◽  
Short Chain Fatty Acids ◽  
Lung Epithelial Cells ◽  
Short Chain ◽  
Lung Epithelial ◽  
Inflammatory Changes ◽  
Chain Fatty Acids

scholarly journals The effects of hedgehog ligand neutralising antibody 5E1 in a mouse model of endometriosis

2020 ◽  
Author(s):  
Fiona L Cousins ◽  
Johanna K Farley ◽  
Rebecca Kerrigan ◽  
Shayanti Mukherjee ◽  
Saeedeh Darzi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Peritoneal Cavity ◽  
Matched Control ◽  
Painful Condition ◽  
Hedgehog Signalling ◽  
Retrograde Menstruation ◽  
Proliferation And Apoptosis ◽  
Endometrial Epithelial Cells

Abstract Objective: Endometriosis is a common and painful condition characterized by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of by endometriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial menstruation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy.Results: Treatment with 5E1, reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis.

High levels of fatty acids inhibit β-casein synthesis through suppression of the JAK2/STAT5 and mTOR signaling pathways in mammary epithelial cells of cows with clinical ketosis

2020 ◽  
Vol 87 (2) ◽  
pp. 212-219 ◽  
Author(s):  
Xin Shu ◽  
Zhiyuan Fang ◽  
Yuan Guan ◽  
Xiying Chen ◽  
Juan J. Loor ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Dairy Cows ◽  
Signaling Pathways ◽  
Milk Protein ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Mtor Signaling ◽  
High Concentrations ◽  
Casein Synthesis

AbstractKetosis is a metabolic disease of dairy cows often characterized by high concentrations of ketone bodies and fatty acids, but low milk protein and milk production. The Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) and the mechanistic target of rapamycin (mTOR) signaling pathways are central for the regulation of milk protein synthesis. The effect of high levels of fatty acids on these pathways and β-casein synthesis are unknown in dairy cows with clinical ketosis. Mammary gland tissue and blood samples were collected from healthy (n = 15) and clinically-ketotic (n = 15) cows. In addition, bovine mammary epithelial cells (BMEC) were treated with fatty acids, methionine (Met) or prolactin (PRL), respectively. In vivo, the serum concentration of fatty acids was greater (P > 0.05) and the percentage of milk protein (P > 0.05) was lower in cows with clinical ketosis. The JAK2-STAT5 and mTOR signaling pathways were inhibited and the abundance of β-casein was lower in mammary tissue of cows with clinical ketosis (P > 0.05). In vitro, high levels of fatty acids inhibited the JAK2-STAT5 and mTOR signaling pathways (P > 0.05) and further decreased the β-casein synthesis (P > 0.05) in BMEC. Methionine or PRL treatment, as positive regulators, activated the JAK2-STAT5 and mTOR signaling pathways to increase the β-casein synthesis. Importantly, the high concentration of fatty acids attenuated the positive effect of Met or PRL on mTOR, JAK2-STAT5 pathways and the abundance of β-casein (P > 0.05). Overall, these data indicate that the high concentrations of fatty acids that reach the mammary cells during clinical ketosis inhibit mTOR and JAK2-STAT5 signaling pathways, and further suppress β-casein synthesis.

scholarly journals Non-Esterified Fatty Acids Over-Activate the TLR2/4-NF-Κb Signaling Pathway to Increase Inflammatory Cytokine Synthesis in Neutrophils from Ketotic Cows

2018 ◽  
Vol 48 (2) ◽  
pp. 827-837 ◽  
Author(s):  
Yuming Zhang ◽  
Xiaobing Li ◽  
Haolong Zhang ◽  
Zhibo Zhao ◽  
Zhicheng Peng ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Signaling Pathway ◽  
Proinflammatory Cytokines ◽  
Pyrrolidine Dithiocarbamate ◽  
Tlr4 Expression ◽  
Blood Concentrations ◽  
Esterified Fatty Acids ◽  
Tnf Α ◽  
High Concentrations

Background/Aims: Dairy cows with clinical ketosis display a negative energy balance and high blood concentrations of non-esterified fatty acids (NEFAs), the latter of which is an important pathological factor of ketosis in cows. The aims of this study were to investigate the inflammatory status of ketotic cows and to determine whether and through what underlying mechanism high levels of NEFAs induce an inflammatory response. Methods: Proinflammatory factors and the nuclear factor kappa B (NF-κB) signaling pathway were evaluated in neutrophils from clinical ketotic and control cows, using methods including western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. In vitro, the effects of NEFAs on the NF-κB signaling pathway in cow neutrophils were also evaluated using the above experimental techniques. Results: Ketotic cows displayed low blood concentrations of glucose and high blood NEFA and β-hydroxybutyrate concentrations. Importantly, Toll-like receptor 2 (TLR2) and TLR4 expression and IκBα and NF-κB p65 phosphorylation levels in neutrophils (PMNs) were significantly higher in ketotic cows than in control cows, indicating over-activation of the TLR2/4-induced NF-κB inflammatory pathway in PMNs in ketotic cows. The blood concentrations of the inflammatory cytokines interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were also significantly increased in ketotic cows. Interestingly, we found that NEFAs were positively correlated with proinflammatory cytokines. In vitro, after pharmacological inhibition of TLR2 and TLR4 expression in cow neutrophils, TLR2 and TLR4 expression was significantly decreased, and the phosphorylation level of NF-κB p65 was also reduced. Cow neutrophils were treated with different concentrations of NEFAs and pyrrolidine dithiocarbamate (PDTC; an NF-κB inhibitor). High concentrations of NEFAs (0.5 and 1 mM) significantly increased TLR2 and TLR4 expression, IκBα and NF-κB p65 phosphorylation levels, NF-κB p65 transcriptional activity, and IL-6, IL-1β, and TNF-α synthesis in cow neutrophils. The inhibition of NF-κB by PDTC suppressed the NEFA-induced synthesis of proinflammatory cytokines. Conclusions: High concentrations of NEFAs can over-activate the TLR2/4-mediated NF-κB signaling pathway to induce the over-production of proinflammatory cytokines, thereby increasing inflammation in cows with clinical ketosis.

327 UNSATURATED AND SATURATED NON-ESTERIFIED FATTY ACIDS DIFFERENTLY AFFECT LIPID STORAGE AND DEVELOPMENTAL COMPETENCE OF BOVINE OOCYTES

2010 ◽  
Vol 22 (1) ◽  
pp. 319
Author(s):  
H. Aardema ◽  
P. Vos ◽  
H. Knijn ◽  
B. Roelen ◽  
B. Gadella
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Palmitic Acid ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Post Partum ◽  
Developmental Competence ◽  
Negative Effects ◽  
Esterified Fatty Acids

Fertility in high-producing dairy cows has declined over the last decades. An increased serum and follicular fluid concentration of non-esterified fatty acids (NEFAs), due to body fat mobilization in the early post partum period, has been postulated as a cause for this fertility decline. NEFA concentrations and composition may change in the environment of the oocyte and thus might affect the storage depots of esterified NEFAs in the oocyte. We exposed COCs to unsaturated (oleic acid) or saturated (palmitic acid) NEFAs during maturation and subsequently examined lipid droplets and developmental competence of the oocytes. COCs from 3-8 mm follicles of slaughterhouse ovaries were cultured in control maturation medium (TCM-199) and medium containing 100, 250, or 500 μM oleic and/or palmitic acid (10 mM fatty acid was bound to 10% BSA fatty acid free). These concentrations were based on in vivo measured NEFA concentrations in follicular fluid in the early post partum period (Leroy et al. 2005 Reproduction 130, 485-495). After 23 h of maturation, COCs were fertilized (450 per group) and cultured till the blastocyst stage, or fixed (80 per group) for lipid droplet staining with C1-BODIPY® 500/510 C12. Confocal microscopy was performed to determine lipid droplet size in (im(mean) and the number of lipid droplets per oocyte. Lipid droplet number and the log of size were analyzed using analysis of variances with condition as fixed factor. Variation was described as the standard error of the mean. Similar concentrations of palmitic or oleic acid had an opposite effect on the size of lipid droplets in oocytes. The number of lipid droplets dramatically decreased in oocytes exposed to 500 μM palmitic acid (178 ± 20), whereas the number increased after exposure to 500 μM oleic acid (554 ± 15). The number of lipid droplets of oocytes exposed to a combination of 250 μM palmitic acid and 250 μM oleic acid (421 ± 23) was comparable with the control and lower oleic and palmitic acid concentrations. Exposure of COCs to palmitic acid during maturation resulted in reduced blastocyst development in a dose-dependent manner (from 18 ± 1.4%, 13 ± 2.4% to 2.8 ± 1.3% after exposure to 500 μM) when compared to control (20 ± 2.2%) or oocytes exposed to oleic acid (from 23 ± 1.6%, 23 ± 3.3% till 28 ± 3.3%). Negative effects of palmitic acid were counteracted by simultaneous exposure to oleic acid during in vitro oocyte maturation (26 ± 5.5%). We conclude that palmitic acid elicited negative effects on early embryonic development, possibly because it induces a reduction in the number of lipid droplets. These adverse effects can be offset by oleic acid during maturation. Moreover a high oleic acid concentration increased the number and size of lipid droplets of oocytes. The regulatory pathways involved in the noted differences in lipid storage features of in vitro-matured oocytes as well as the adverse effects of palmitic acid on early embryonic development are currently under research.

Estradiol-17β regulates proliferation and apoptosis of sheep endometrial epithelial cells by regulating the relative abundance of YAP1

2020 ◽  
Vol 215 ◽  
pp. 106328
Author(s):  
Shi-Yu An ◽  
Xiao-Xiao Gao ◽  
Zhi-Bo Wang ◽  
Ya-Xu Liang ◽  
Shu-Ting Wang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Relative Abundance ◽  
Proliferation And Apoptosis ◽  
Estradiol 17Β ◽  
Endometrial Epithelial Cells

Comparative toxicity of fatty acids on a macrophage cell line (J774)

2006 ◽  
Vol 111 (5) ◽  
pp. 307-317 ◽  
Author(s):  
Thais Martins de Lima ◽  
Maria Fernanda Cury-Boaventura ◽  
Gisele Giannocco ◽  
Maria Tereza Nunes ◽  
Rui Curi
Keyword(s):  
Fatty Acids ◽  
Cell Death ◽  
Cell Line ◽  
Lipid Accumulation ◽  
Membrane Integrity ◽  
Peroxisome Proliferator ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Peroxisome Proliferator Activated Receptor ◽  
High Concentrations

In the present study, the cytotoxicity of palmitic, stearic, oleic, linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids on a macrophage cell line (J774) was investigated. The induction of toxicity was investigated by changes in cell size, granularity, membrane integrity, DNA fragmentation and phosphatidylserine externalization by using flow cytometry. Fluorescence microscopy was used to determine the type of cell death (Acridine Orange/ethidium bromide assay). The possible mechanisms involved were examined by measuring mitochondrial depolarization, lipid accumulation and PPARγ (peroxisome-proliferator-activated receptor γ) activation. The results demonstrate that fatty acids induce apoptosis and necrosis of J774 cells. At high concentrations, fatty acids cause macrophage death mainly by necrosis. The cytotoxicity of the fatty acids was not strictly related to the number of double bonds in the molecules: palmitic acid>docosahexaenoic acid>stearic acid=eicosapentaenoic acid=arachidonic acid>oleic acid>linoleic acid. The induction of cell death did not involve PPARγ activation. The mechanisms of fatty acids to induce cell death involved changes in mitochondrial transmembrane potential and intracellular neutral lipid accumulation. Fatty acids poorly incorporated into triacylglycerol had the highest toxicity.

Embryonic regulation of IL-8 production and secretion in human endometrial epithelial cells

1998 ◽  
Vol 5 (1) ◽  
pp. 117A-117A ◽  
Author(s):  
P CABALLEROCAMPO ◽  
A BERNAL ◽  
A MERCADER ◽  
E OCONNOR ◽  
J COLOMA ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Embryonic Regulation ◽  
Endometrial Epithelial Cells
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