Effects of EPA and DHA on lipid droplet accumulation and mRNA abundance of PAT proteins in caprine monocytes

Lecchi, Cristina; Invernizzi, G.; Agazzi, Alessandro; Modina, S.; Sartorelli, P.; Savoini, G.; Ceciliani, Fabrizio

doi:10.1016/j.rvsc.2012.09.019

Cited by 21 publications

(18 citation statements)

References 46 publications

(52 reference statements)

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“…Since we observed significant dose-dependent increases in TAG and CholE content in response to irradiation and GLA treatment, we analyzed the possible changes in the expression of a lipid binding protein, PLIN3. Perilipins are a multi-protein family that target LD surfaces and regulate lipid storage and hydrolysis [70]. In good accord with the increased TAG content of treated cells, we found that irradiation (both 5 and 10 Gy) significantly induced PLIN3 gene expression in U87 MG cells on incubation for 48 h (Fig.…”

Section: Discussionsupporting

confidence: 77%

Lipidomic analysis reveals a radiosensitizing role of gamma-linolenic acid in glioma cells

Antal

Péter

Hackler³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Previous studies have demonstrated that gamma-linolenic acid (GLA) is effective against glioma cells under both in vitro and in vivo conditions. In the present study we determined how GLA alone or in combination with irradiation alters the fatty acid (FA) and lipid profiles, the lipid droplet (LD) content, the lipid biosynthetic gene expression and the apoptosis of glioma cells. In GLA-treated cells direct correlations were found between the levels of various FAs and the expression of the corresponding FA biosynthetic genes. The total levels of saturated and monosaturated FAs decreased in concert with the down-regulation of FASN and SCD1 gene expression. Similarly, decreased FADS1 gene expression was paralleled by lowered arachidonic acid (20:4 n-6) and eicosapentaenoic acid (20:5 n-3) contents, while the down-regulation of FADS2 expression was accompanied by a diminished docosahexaenoic acid (22:6 n-3) content. Detailed mass spectrometric analyses revealed that individual treatments gave rise to distinct lipidomic fingerprints. Following uptake, GLA was subjected to elongation, resulting in dihomo-gamma-linolenic acid (20:3 n-6, DGLA), which was used for the synthesis of the LD constituent triacylglycerols and cholesteryl esters. Accordingly, an increased number of LDs were observed in response to GLA administration after irradiation. GLA increased the radioresponsiveness of U87 MG cells, as demonstrated by an increase in the number of apoptotic cells determined by FACS analysis. In conclusion, treatment with GLA increased the apoptosis of irradiated glioma cells, and GLA might therefore increase the therapeutic efficacy of irradiation in the treatment of gliomas.

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Section: Discussionsupporting

confidence: 77%

Lipidomic analysis reveals a radiosensitizing role of gamma-linolenic acid in glioma cells

Antal

Péter

Hackler³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…LBs are organelles found in almost all eukaryotic cells, and their number and size vary in different cell types [ 25 , 26 ]. LBs were thought for many years to be storage sites for lipids; now they are beginning to emerge as dynamic organelles and signaling platforms affecting cell fate [ 27 , 28 ]. However the exact role of LBs in neural cell survival and maintenance of neural circuitries is unclear.…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic acid (DHA): a modulator of microglia activity and dendritic spine morphology

Chang

Khatchadourian

McKinney

et al. 2015

J Neuroinflammation

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BackgroundRecent studies have revealed that excessive activation of microglia and inflammation-mediated neurotoxicity are implicated in the progression of several neurological disorders. In particular, chronic inflammation in vivo and exposure of cultured brain cells to lipopolysaccharide (LPS) in vitro can adversely change microglial morphology and function. This can have both direct and indirect effects on synaptic structures and functions. The integrity of dendritic spines, the postsynaptic component of excitatory synapses, dictates synaptic efficacy. Interestingly, dysgenesis of dendritic spines has been found in many neurological diseases associated with ω-3 polyunsaturated fatty acid (PUFA) deficiency and cognitive decline. In contrast, supplemented ω-3 PUFAs, such as docosahexaenoic acid (DHA), can partly correct spine defects. Hence, we hypothesize that DHA directly affects synaptic integrity and indirectly through neuron-glia interaction. Strong activation of microglia by LPS is accompanied by marked release of nitric oxide and formation of lipid bodies (LBs), both dynamic biomarkers of inflammation. Here we investigated direct effects of DHA on synaptic integrity and its indirect effects via microglia in the hippocampal CA1 region.MethodsMicroglia (N9) and organotypic hippocampal slice cultures were exposed to the proinflammagen LPS (100 ng/ml) for 24 h. Biochemical and morphological markers of inflammation were investigated in microglia and CA1 regions of hippocampal slices. As biomarkers of hyperactive microglia, mitochondrial function, nitric oxide release and LBs (number, size, LB surface-associated proteins) were assessed. Changes in synaptic transmission of CA1 pyramidal cells were determined following LPS and DHA (25-50 μM) treatments by recording spontaneous AMPA-mediated miniature excitatory postsynaptic currents (mEPSCs).ResultsMicroglia responded to LPS stimulation with a significant decrease of mitochondrial function, increased nitric oxide production and an increase in the formation of large LBs. LPS treatment led to a significant reduction of dendritic spine densities and an increase in the AMPA-mediated mEPSC inter-event interval (IEI). DHA normalized the LPS-induced abnormalities in both neurons and microglia, as revealed by the restoration of synaptic structures and functions in hippocampal CA1 pyramidal neurons.ConclusionOur findings indicate that DHA can prevent LPS-induced abnormalities (neuroinflammation) by reducing inflammatory biomarkers, thereby normalizing microglia activity and their effect on synaptic function.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0244-5) contains supplementary material, which is available to authorized users.

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“…However, as the analysis of transcriptome goes on, we found two other key genes, PLIN1 and PLIN2, which may have an important regulatory effect on PPAR signaling pathway. PLIN1 and PLIN2 are both the members of PAT protein family which is a key protein that regulates the formation of lipid droplet [ 37 , 38 ]. Previous researches demonstrated that phosphorylated PLIN1 activated lipolytic activity and hydrolysis of triacylglycerides [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of hepatic transcriptome demonstrates altered lipid metabolism following Lactobacillus johnsonii BS15 prevention in chickens with subclinical necrotic enteritis

et al. 2018

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BackgroundSubclinical necrotic enteritis (SNE) widely outbreaks in chickens which inflicted growth-slowing, causing enormous social and economic burdens. To better understand the molecular underpinnings of SNE on lipid metabolism and explore novel preventative strategies against SNE, we studied the regulatory mechanism of a potential probiotic, Lactobacillus johnsonii BS15 on the lipid metabolism pathways involved in chickens with SNE.MethodsOne hundred eighty one-day-old chickens were randomly divided into three groups and arranged with basal diet (control and SNE group). Added with BS15 (1 × 106 cfu/g) or Man Rogosa Sharpe (MRS) liquid medium for 28 days. The hepatic gene expression of each group was then measured using high-throughput analysis methods (RNA-Seq). Quantitative real-time PCR (qRT-PCR) was used to detect the expression changes of the related genes.ResultsThe results showed that there are eleven lipid metabolic pathways were found during the prevention of BS15 treatment in SNE chickens by RNA-Seq, including the peroxisome proliferator-activated receptor (PPAR) signaling pathway and arachidonic acid metabolism. BS15 notably facilitated the expressions of fatty acid binding protein 2 (FABP2), acyl-CoA synthetase bubblegum family member 1 (ACSBG1), perilipin 1 (PLIN1) and perilipin 2 (PLIN2), which were involved in PPAR signaling pathway of SNE chickens. Besides, suppression of phospholipase A2 group IVA (PLA2G4A) in arachidonic acid metabolism was observed in SNE chickens after BS15 prevention. The expression patterns of FABP2, ACSBG1, PLIN1, PLIN2 and PLA24G in qRT-PCR validation were consistent with RNA-Seq results.ConclusionsThese findings indicate that SNE may affect the hepatic lipid metabolism of chickens. Meanwhile, BS15 pretreatment may provide a prospective natural prophylaxis strategy against SNE through improving the PPAR signaling pathway and arachidonic acid metabolism.Electronic supplementary materialThe online version of this article (10.1186/s12944-018-0741-5) contains supplementary material, which is available to authorized users.

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Effects of EPA and DHA on lipid droplet accumulation and mRNA abundance of PAT proteins in caprine monocytes

Cited by 21 publications

References 46 publications

Lipidomic analysis reveals a radiosensitizing role of gamma-linolenic acid in glioma cells

Lipidomic analysis reveals a radiosensitizing role of gamma-linolenic acid in glioma cells

Docosahexaenoic acid (DHA): a modulator of microglia activity and dendritic spine morphology

Analysis of hepatic transcriptome demonstrates altered lipid metabolism following Lactobacillus johnsonii BS15 prevention in chickens with subclinical necrotic enteritis

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