Supplementation with linoleic acid‐rich soybean oil stimulates macrophage foam cell formation via increased oxidative stress and diacylglycerol acyltransferase1‐mediated triglyceride biosynthesis

Rom, Oren; Jeries, Helana; Hayek, Tony; Aviram, Michael

doi:10.1002/biof.1319

Cited by 14 publications

(26 citation statements)

References 51 publications

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“…Among them, samples 14 and 15 (both of Brazilian origin) were distinctive in composition compared to the other omega-3 supplements since they presented low levels of EPA and DHA, and high levels of linoleic acid (LA, 18:2n-6). Thus, since soybean oil has in its composition mainly LA, 22 the same fatty acids were quantified in this vegetable oil in order to compare their contents with those found in samples 14 and 15; and the results are presented in Table 2.…”

Section: Fatty Acid Compositionmentioning

confidence: 99%

Quality Assessment of Omega-3 Supplements Available in the Brazilian Market

Galuch¹,

Carbonera²,

Magon³

et al. 2017

J. Braz. Chem. Soc.

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Omega-3 fish oil supplements are widely consumed as source of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, presenting beneficial effects on human health. This study aimed to evaluate fifteen brands of omega-3 fish oil supplements available in Brazilian market in order to estimate the Brazilian reality regarding those supplements. Twelve fatty acids were quantified by gas chromatography with a flame ionization detector (GC-FID), and lipid profile were obtained via mass spectrometry fingerprinting using direct electrospray ionization mass spectrometry (ESI-MS) to assess the form in which fatty acids are present as well as the possible fraud existence. Among all analyzed samples, thirteen brands were revealed as EPA and DHA sources (90.2-440.3 and 77.8-302.3 mg g -1 lipid, respectively) in triacylglycerols (TAG) or ethyl esters (EE) form. However, two brands were discovered with addition of large amounts of soybean oil, leading the final consumer to ingest this low-cost oil believing that they are consuming adequate doses of EPA and DHA.

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Section: Fatty Acid Compositionmentioning

confidence: 99%

Quality Assessment of Omega-3 Supplements Available in the Brazilian Market

Galuch¹,

Carbonera²,

Magon³

et al. 2017

J. Braz. Chem. Soc.

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“…Collectively these data indicate that 20-HETE is capable of modulating endogenously expressed TRPC6 channels of podocytes. We have previously shown that currents with similar properties are activated by exposing podocytes to a membrane-permeable diacylglycerol analog (OAG) (Anderson et al, 2013; Kim et al, 2013). Here we observed that 100 μM OAG evoked an additional increase in currents in podocytes after prior activation of TRPC6 by 20 μM 20-HETE.…”

Section: Resultsmentioning

confidence: 99%

“…Podocyte differentiation and expression of podocyte markers were induced by removal of γ-interferon and raising temperature to 37°C for 14 days. TRPC6 siRNA, podocin siRNA and non-targeting control siRNA were transfected into differentiated MPC-5 cells after isolation using Lipofectamine 3000™ (Invitrogen) in serum-reduced medium according to the manufacturer's directions (Anderson et al, 2013). Electrophysiological and biochemical analyses were carried out 24 h after transfection with siRNAs.…”

Section: Methodsmentioning

confidence: 99%

“…Methods for conventional whole-cell recordings from podocytes were carried out by standard methods that have been described in detail previously (Anderson et al, 2013, 2014; Roshanravan and Dryer, 2014). Recordings were made with an Axopatch 1D amplifier (Molecular Devices) and analyzed using pClamp™ v 10 software (Molecular Devices).…”

Section: Methodsmentioning

confidence: 99%

“…Within podocytes, TRPC6 channels are located in the cholesterol-rich slit diaphragm domains of foot processes, as well as in major processes, and in the cell body (Reiser et al, 2005; Huber et al, 2006; Dryer and Reiser, 2010). TRPC6 channels in foot processes are components of large super-complexes that include podocin, nephrin, NADPH oxidases, phospholipases, and tyrosine kinases (Reiser et al, 2005; Huber et al, 2006; Kanda et al, 2011; Anderson et al, 2013; Kim et al, 2013; Kalwa et al, 2015; Rinschen et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

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20-Hydroxyeicosatetraenoic Acid (20-HETE) Modulates Canonical Transient Receptor Potential-6 (TRPC6) Channels in Podocytes

2016

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The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) regulates renal function, including changes in glomerular function evoked during tubuloglomerular feedback (TGF). This study describes the cellular actions of 20-HETE on cultured podocytes, assessed by whole-cell recordings from cultured podocytes combined with pharmacological and cell-biological manipulations of cells. Bath superfusion of 20-HETE activates cationic currents that are blocked by the pan-TRP blocker SKF-96365 and by 50 μM La3+, and which are attenuated after siRNA knockdown of TRPC6 subunits. Similar currents are evoked by a membrane-permeable analog of diacylgycerol (OAG), but OAG does not occlude responses to maximally-activating concentrations of 20-HETE (20 μM). Exposure to 20-HETE also increased steady-state surface abundance of TRPC6 subunits in podocytes as assessed by cell-surface biotinylation assays, and increased cytosolic concentrations of reactive oxygen species (ROS). TRPC6 activation by 20-HETE was eliminated in cells pretreated with TEMPOL, a membrane-permeable superoxide dismutase mimic. Activation of TRPC6 by 20-HETE was also blocked when whole-cell recording pipettes contained GDP-βS, indicating a role for either small or heterotrimeric G proteins in the transduction cascade. Responses to 20-HETE were eliminated by siRNA knockdown of podocin, a protein that organizes NADPH oxidase complexes with TRPC6 subunits in this cell type. In summary, modulation of ionic channels in podocytes may contribute to glomerular actions of 20-HETE.

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Leucine supplementation attenuates macrophage foam‐cell formation: Studies in humans, mice, and cultured macrophages

et al. 2018

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Whereas atherogenicity of dietary lipids has been largely studied, relatively little is known about the possible contribution of dietary amino acids to macrophage foam-cell formation, a hallmark of early atherogenesis. Recently, we showed that leucine has antiatherogenic properties in the macrophage model system. In this study, an in-depth investigation of the role of leucine in macrophage lipid metabolism was conducted by supplementing humans, mice, or cultured macrophages with leucine. Macrophage incubation with serum obtained from healthy adults supplemented with leucine (5 g/d, 3 weeks) significantly decreased cellular cholesterol mass by inhibiting the rate of cholesterol biosynthesis and increasing cholesterol efflux from macrophages. Similarly, leucine supplementation to C57BL/6 mice (8 weeks) resulted in decreased cholesterol content in their harvested peritoneal macrophages (MPM) in relation with reduced cholesterol biosynthesis rate. Studies in J774A.1 murine macrophages revealed that leucine dose-dependently decreased cellular cholesterol and triglyceride mass. Macrophages treated with leucine (0.2 mM) showed attenuated uptake of very low-density lipoproteins and triglyceride biosynthesis rate, with a concurrent down-regulation of diacylglycerol acyltransferase-1, a key enzyme catalyzing triglyceride biosynthesis in macrophages. Similar effects were observed when macrophages were treated with α-ketoisocaproate, a key leucine metabolite. Finally, both in vivo and in vitro leucine supplementation significantly improved macrophage mitochondrial respiration and ATP production. The above studies, conducted in human, mice, and cultured macrophages, highlight a protective role for leucine attenuating macrophage foam-cell formation by mechanisms related to the metabolism of cholesterol, triglycerides, and energy production. © 2018 BioFactors, 44(3):245-262, 2018.

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Supplementation with linoleic acid‐rich soybean oil stimulates macrophage foam cell formation via increased oxidative stress and diacylglycerol acyltransferase1‐mediated triglyceride biosynthesis

Cited by 14 publications

References 51 publications

Quality Assessment of Omega-3 Supplements Available in the Brazilian Market

Quality Assessment of Omega-3 Supplements Available in the Brazilian Market

20-Hydroxyeicosatetraenoic Acid (20-HETE) Modulates Canonical Transient Receptor Potential-6 (TRPC6) Channels in Podocytes

Leucine supplementation attenuates macrophage foam‐cell formation: Studies in humans, mice, and cultured macrophages

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