Eicosapentaenoic acid suppresses palmitate-induced cytokine production by modulating long-chain acyl-CoA synthetase 1 expression in human THP-1 macrophages

Nakakuki, Masanori; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori

doi:10.1016/j.atherosclerosis.2012.12.036

Cited by 23 publications

(19 citation statements)

References 30 publications

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“…Functionally, ACSL1 has been implicated in pathways of neutral lipid synthesis as well as in both mitochondrial in the heart and peroxisomal β-oxidation in the liver and adipose tissue (Coleman et al, 2002;Nakakuki et al, 2013). Supplementation of DHA-G downregulated ACSL1 expression in both SAT and PAT; however, no correlation was observed between miR-142-5p and ASCL1, despite a significant downregulation of miR-142-5p in both subcutaneous and visceral fat when DHA-G was included in the diet.…”

Section: Discussionmentioning

confidence: 67%

Effect of diet on microRNA expression in ovine subcutaneous and visceral adipose tissues1

Meale

Romao

et al. 2014

Journal of Animal Science

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Knowledge of the molecular mechanisms that regulate ovine adipogenesis is very limited. MicroRNAs (miRNA) have been reported as one of the regulatory mechanisms of adipogenesis. This study aimed to compare the expression of miRNA related to ovine adipogenesis in different adipose depots and to investigate whether their expression is affected by dietary fatty acid composition. We also investigated the role of miRNA in adipogenic gene regulation. Subcutaneous and visceral adipose tissue samples were collected at slaughter from 12 Canadian Arcott lambs fed a barley-based finishing diet where an algae meal (DHA-Gold; Schizochytrium spp.) replaced flax oil and barley grain at 0 or 3% DM (n = 6). Total RNA from each tissue was subjected to quantitative real time (qRT-) PCR analysis to determine the expression of 15 selected miRNA including 11 identified from bovine adipose tissues and 4 conserved between bovine and ovine species. MicroRNAs were differentially expressed according to diet in each tissue depot (miR-142-5p and miR-376d) in visceral and miR-142-5p, miR92a, and miR-378 in subcutaneous adipose tissue; P ≤ 0.05) and in each tissue depot depending on diet (miR-101, miR-106, miR-136, miR-16b, miR-196a-1, miR-2368*, miR-2454, miR-296, miR-376d, miR-378, and miR-92a in both control and DHA-G diets and miR-478 in control; P ≤ 0.05). Six miRNA were subjected to functional analysis and 3 genes of interest (ACSL1, PPARα, and C/EBPα) were validated by qRT-PCR. Both diet and tissue depot affected expression levels of all 3 genes (P < 0.05). miR-101, miR-106, and miR-136 were negatively correlated with their respective predicted gene targets C/ EBPα, PPARα, and ACSL1 in subcutaneous adipose tissue of lambs fed DHA-G. Yet miR-142-5p and miR-101 showed no correlation with ACSL1 or C/EBPα. The variability in expression patterns of miRNA across adipose depots reflects the tissue specific nature of adipogenic regulation. Although the examined miRNA appear to be conserved across ruminant species, our results indicate the presence of ovine specific regulatory mechanisms that can be influenced by diet.

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Section: Discussionmentioning

confidence: 67%

Effect of diet on microRNA expression in ovine subcutaneous and visceral adipose tissues1

Meale

Romao

et al. 2014

Journal of Animal Science

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“…Triacsin C is known to inhibit ACSL1, 3, and 4 activation 26) . In macrophages and vascular smooth muscle cells, the expression of at least ACSL1, 3, and 4 has been confirmed, and it is known that PA induces ACSL expression in these cells 11,12) . In this study, we demonstrated that PA augmented the expression of ACSL isoforms in vascular endothelial cells as well, in particular ACSL3, while EPA inhibited the increase in their expressions (Fig.…”

Section: Discussionmentioning

confidence: 84%

“…Because p21 expression was not attenuated by IKK inhibitor in our investigation, the PAinduced increase in p21 expression may be a factor independent of the IKK-NF-kB pathway. It has been demonstrated that in THP-1 macrophages, PA stimulates the phosphorylation of p38 MAPK while EPA inhibits it 11) , and EPA has also been shown to inhibit LPS-induced AP-1 activation 34) . Therefore, the changes in p21 expression in vascular endothelial cells induced by PA or EPA are consistent with previous reports.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, an excess of saturated fatty acids is considered a risk factor for cardiovascular disease and has been reported to trigger inflammatory signals in various tissues and promote lipotoxicity 10) . In order to elucidate the mechanism of the anti-atherogenic effect of EPA, we studied lipotoxicity in vascular cells and showed that palmitic acid (PA), a major saturated fatty acid in plasma, stimulates inflammatory cytokine production in macrophages as well as osteoblastic differentiation of vascular smooth muscle cells, and that this action could be mediated by long-chain acyl-CoA synthetase (ACSL), an enzyme that converts free fatty acids into acyl-CoA derivatives 11,12) . Furthermore, we also reported that EPA may ameliorate lipotoxicity in macrophages and vascular smooth muscle cells through the common mechanism of ACSL expression regulation.…”

Section: Elisamentioning

confidence: 99%

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Eicosapentaenoic Acid Prevents Saturated Fatty Acid-Induced Vascular Endothelial Dysfunction: Involvement of Long-Chain Acyl-CoA Synthetase

Ishida

Naoe

Nakakuki

et al. 2015

J Atheroscler Thromb

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Aim: Vascular endothelial dysfunction is considered an early predictor of atherosclerosis. It has been proven that elevated blood levels of free fatty acids pose a substantial risk for the development of cardiovascular disease. In this study, we examined the effects of palmitic acid (PA), a saturated fatty acid, on endothelial function by using the expression of adhesion molecule, cytokines, and inflammatory protein as indicators, as well as investigated the effects of eicosapentaenoic acid, an n-3 polyunsaturated fatty acid. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to PA and EPA. Results: When HUVEC were exposed to PA, there was an increase in the expression of adhesion molecule, cytokines, and inflammatory protein (ICAM-1, MCP-1, interleukin-6, PTX3). PA augmented the expression of long-chain acyl-CoA synthetase (ACSL) and the cyclin-dependent kinase inhibitor p21, and enhanced the phosphorylation of p65, a component of NF-B. ACSL inhibition and siRNA-mediated ACSL3 knockdown suppressed the PA-induced increase in the expression of adhesion molecule, cytokines, and inflammatory protein, and ACSL inhibition suppressed the enhancement of p65 phosphorylation. In addition, p21 knockdown suppressed the PA-induced increase in the expression of MCP-1 and ICAM-1. EPA suppressed the PA-induced increase in the expression of ACSL and p21, the enhancement of p65 phosphorylation, as well as the associated increase in the expression of ICAM-1, MCP-1, interleukin-6, and PTX3. Conclusions: These results suggest that the ACSL, p21, and NF-B-dependent pathway may possibly be involved in PA-induced vascular endothelial dysfunction, and that EPA ameliorates this at least in part through the regulation of ACSL3 expression.

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“…TNF␣, IL6, and CXCL1/KC) (12)(13)(14). Conversely, polyunsaturated fatty acids suppress these inflammatory effects on monocytes/macrophages (15)(16)(17)(18)(19)(20). A recent study ascribed this protection to activation of AMP-activated protein kinase (AMPK) 6 (21), and, indeed, AMPK activation in vitro and in vivo correlates with macrophage skewing toward an M2 phenotype (22)(23)(24).…”

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confidence: 99%

Palmitoleate Reverses High Fat-induced Proinflammatory Macrophage Polarization via AMP-activated Protein Kinase (AMPK)

Chan

Pillon

Sivaloganathan

et al. 2015

Journal of Biological Chemistry

160

171

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Background: Elevated saturated fats during obesity activate proinflammatory pathways in macrophages, contributing to insulin resistance. Results: The monounsaturated fatty acid cis-palmitoleate antagonizes saturated fat-induced proinflammatory macrophage polarization through an AMPK-dependent mechanism. Conclusion: Palmitoleate is a lipid mediator that confers an anti-inflammatory macrophage phenotype. Significance: Understanding lipid-mediated macrophage polarization is critical to develop nutritional or cell-based strategies to combat insulin resistance.

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Eicosapentaenoic acid suppresses palmitate-induced cytokine production by modulating long-chain acyl-CoA synthetase 1 expression in human THP-1 macrophages

Cited by 23 publications

References 30 publications

Effect of diet on microRNA expression in ovine subcutaneous and visceral adipose tissues1

Effect of diet on microRNA expression in ovine subcutaneous and visceral adipose tissues1

Eicosapentaenoic Acid Prevents Saturated Fatty Acid-Induced Vascular Endothelial Dysfunction: Involvement of Long-Chain Acyl-CoA Synthetase

Palmitoleate Reverses High Fat-induced Proinflammatory Macrophage Polarization via AMP-activated Protein Kinase (AMPK)

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