Omega-3 polyunsaturated fatty acids suppress the inflammatory responses of lipopolysaccharide-stimulated mouse microglia by activating SIRT1 pathways

Inoue, Takayuki; Tanaka, Masashi; Masuda, Shinji; Ohue‐Kitano, Ryuji; Yamakage, Hajime; Muranaka, Kazuya; Wada, Hiromichi; Kusakabe, Toru; Shimatsu, Akira; Hasegawa, Koji; Satoh‐Asahara, Noriko

doi:10.1016/j.bbalip.2017.02.010

Cited by 93 publications

(70 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While SFA mainly act as pro‐inflammatory stimuli (Z. Wang et al, ; Gao et al, ), N‐3 PUFAs and their metabolites have emerged as anti‐inflammatory modulators of microglial functions (Laye, Nadjar, Joffre, & Bazinet, ). Independent of the inflammatory challenge applied (e.g., hypoxia, interferon‐y, amyloid‐β), cultured microglia consistently show decreased production of pro‐inflammatory factors (De Smedt‐Peyrusse et al, ), decreased COX2 and iNOS activity (Pettit, Varsanyi, Tadros, & Vassiliou, ; Zendedel et al, ) while exibit typical features of anti‐inflammatory microglia, like CD206 surface expression and autophagy when treated with n‐3 PUFAs (Chhor et al, ; Inoue et al, ). Many in vivo studies confirm that N‐3 PUFA supplementation reduces detrimental microglia function (summarized in (Laye et al, ).…”

Section: Alimentary Components Driving Pro‐regenerative Microglia Funmentioning

confidence: 99%

“…Molecular pathways for the anti‐inflammatory effects of N‐3 PUFAs include activation and overexpression of the protein deacetylase sirtuin1 (SIRT1), with subsequent suppression of NF‐κB via subunit p65 deacetylation (Figure ); (Inoue et al, ). Inhibition of p38MAPK inflammatory pathway and PPAR‐γ activation are also in part responsible of protective effects of PUFAs and their products (Antonietta Ajmone‐Cat et al, ; De Smedt‐Peyrusse et al, ).…”

Section: Alimentary Components Driving Pro‐regenerative Microglia Funmentioning

confidence: 99%

“…SIRTs are a family of NAD‐dependent lysine deacetylases, that play a key role in regulation of cellular metabolism among other fundamental cell function. SIRT1 and SIRT6 were reported to coordinate a switch from glycolysis to fatty acid oxidation in macrophages (J. Yu & Auwerx, ) and SIRT1 and 2 were shown to prevent excessive microglia activation through NF‐κB deacetylation (Figure ); (L. Li et al, ); (Inoue et al, ; Pais et al, ). Starting from Resveratrol, the first SIRT1activator described, other SIRT activators have been developed and some of them are currently in clinical trials for the treatment of age‐related neuroinflammation (Carafa et al, ).…”

Section: Metabolic Drugs and Molecular Pathways Which May Be Exploitementioning

confidence: 99%

See 2 more Smart Citations

How to reprogram microglia toward beneficial functions

Fumagalli

Lombardi

Gressèns

et al. 2018

Glia

View full text Add to dashboard Cite

Microglia, brain cells of nonneural origin, orchestrate the inflammatory response to diverse insults, including hypoxia/ischemia or maternal/fetal infection in the perinatal brain. Experimental studies have demonstrated the capacity of microglia to recognize pathogens or damaged cells activating a cytotoxic response that can exacerbate brain damage. However, microglia display an enormous plasticity in their responses to injury and may also promote resolution stages of inflammation and tissue regeneration. Despite the critical role of microglia in brain pathologies, the cellular mechanisms that govern the diverse phenotypes of microglia are just beginning to be defined. Here we review emerging strategies to drive microglia toward beneficial functions, selectively reporting the studies which provide insights into molecular mechanisms underlying the phenotypic switch. A variety of approaches have been proposed which rely on microglia treatment with pharmacological agents, cytokines, lipid messengers, or microRNAs, as well on nutritional approaches or therapies with immunomodulatory cells. Analysis of the molecular mechanisms relevant for microglia reprogramming toward pro-regenerative functions points to a central role of energy metabolism in shaping microglial functions. Manipulation of metabolic pathways may thus provide new therapeutic opportunities to prevent the deleterious effects of inflammatory microglia and to control excessive inflammation in brain disorders.

show abstract

Section: Alimentary Components Driving Pro‐regenerative Microglia Funmentioning

confidence: 99%

Section: Alimentary Components Driving Pro‐regenerative Microglia Funmentioning

confidence: 99%

Section: Metabolic Drugs and Molecular Pathways Which May Be Exploitementioning

confidence: 99%

See 1 more Smart Citation

How to reprogram microglia toward beneficial functions

Fumagalli

Lombardi

Gressèns

et al. 2018

Glia

View full text Add to dashboard Cite

show abstract

“…C), a parameter being inversely correlated with the NAD + /NADH ratios achieved. Interestingly, rats supplemented with DHA alone also exhibited enhanced hepatic NAD + /NADH ratios and liver SIRT1 activity, a novel finding that has been documented under inflammatory conditions in lipopolysaccharide (LPS)‐stimulated mouse microglia . In this latter case, EPA plus DHA suppressed LPS‐induced inflammation by enhancing the mRNA expression of SIRT1 and NAMPT, with increased NAD + levels and SIRT1 activity deacetylating nuclear factor‐κB (NF‐κB) at Lis310 of the p65 subunit, thus diminishing its activity and TNF‐α and IL‐6 generation .…”

Section: Discussionmentioning

confidence: 85%

Docosahexaenoic acid‐thyroid hormone combined protocol as a novel approach to metabolic stress disorders: Relation to mitochondrial adaptation via liver PGC‐1α and sirtuin1 activation

et al. 2018

View full text Add to dashboard Cite

Docosahexaenoic acid (DHA) and 3,3′,5‐triiodothyronine (T3) combined protocol affords protection against liver injury via AMPK signaling supporting energy requirements. The aim of this work was to test the hypothesis that a DHA + T3 accomplish mitochondrial adaptation through downstream upregulation of PPAR‐γ coactivator 1α (PGC‐1α). Male Sprague–Dawley rats were given daily oral doses of 300 mg DHA/kg or saline (controls) for three consecutive days, followed by 0.05 mg T3/kg (or hormone vehicle) ip at the fourth day, or single dose of 0.1 mg T3/kg alone. Liver mRNA levels were assayed by qPCR, NAD+/NADH ratios, hepatic proteins, histone 3 acetylation and serum T3 and β‐hydroxybutyrate levels were determined by specific ELISA kits. Combined DHA + T3 protocol led to increased liver AMPK, PGC‐1α, NRF‐2, COX‐IV, and β‐ATP synthase mRNAs, with concomitant higher protein levels of COX‐IV and NRF‐2, 369% enhancement in the NAD+/NADH ratio, 47% decrease in histone 3 acetylation and 162% increase in serum levels of β‐hydroxybutyrate over control values. These changes were reproduced by the higher dose of T3 without major alterations by DHA or T3 alone. In conclusion, liver mitochondrial adaptation by DHA + T3 is associated with PGC‐1α upregulation involving enhanced transcription of the coactivator, which may be contributed by PGC‐1α deacetylation and phosphorylation by SIRT1 and AMPK activation, respectively. This contention is supported by NRF‐2‐dependent enhancement in COX‐1 and β‐ATP synthase induction with higher fatty acid oxidation resulting in a significant ketogenic response, which may represent a suitable strategy for hepatic steatosis with future clinical applications. © 2018 BioFactors, 45(2):271–278, 2019

show abstract

“…Studies performed in LPS-stimulated mouse microglial cells assessed the mechanism of action of EPA, DHA, and PUFAs. The data demonstrated that these three active ingredients of Omega 3 activate the SIRT1 pathway by inhibiting NF-κB and reducing IL-6 and TNF-α expression [96]. Clinical investigations have revealed that patients who receive an omega 3 treatment demonstrated a suppression in arachidonic acid [97, 98].…”

Section: Natural Anti-inflammatory Compounds To Modulate Inflammatmentioning

confidence: 99%

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

Yanez

Blanchette

Jabbarzadeh

2018

CPD

View full text Add to dashboard Cite

Tissue engineering offers a promising strategy to restore injuries resulting from trauma, infection, tumor resection, or other diseases. In spite of significant progress, the field faces a significant bottleneck; the critical need to understand and exploit the interdependencies of tissue healing, angiogenesis, and inflammation. Inherently, the balance of these interacting processes is affected by a number of injury site conditions that represent a departure from physiological environment, including reduced pH, increased concentration of free radicals, hypoglycemia, and hypoxia. Efforts to harness the potential of immune response as a therapeutic strategy to promote tissue repair have led to the identification of natural compounds with significant anti-inflammatory properties. This article provides a concise review of the body’s inflammatory response to biomaterials and describes the role of oxygen as a physiological cue in this process. We proceed to highlight the potential of natural compounds to mediate inflammatory response and improve host-graft integration. Herein, we discuss the use of natural compounds to map signaling molecules and checkpoints that regulate the cross-linkage of immune response and skeletal repair.

show abstract

Omega-3 polyunsaturated fatty acids suppress the inflammatory responses of lipopolysaccharide-stimulated mouse microglia by activating SIRT1 pathways

Cited by 93 publications

References 40 publications

How to reprogram microglia toward beneficial functions

How to reprogram microglia toward beneficial functions

Docosahexaenoic acid‐thyroid hormone combined protocol as a novel approach to metabolic stress disorders: Relation to mitochondrial adaptation via liver PGC‐1α and sirtuin1 activation

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

Contact Info

Product

Resources

About