Mechanisms by which fatty acids regulate leucocyte function

Lima, Thaís Martins de; Gorjão, Renata; Hatanaka, Elaine; Cury-Boaventura, Maria Fernanda; Silva, Érica Paula Portioli; Procópio, Joaquim; Curi, Rui

doi:10.1042/cs20070006

Cited by 65 publications

(45 citation statements)

References 146 publications

(181 reference statements)

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“…eicosanoids, diacylglycerols, lysophosphatidic acids) and ER stress, which itself can induce JNK phosphorylation and NF-κB activation in cells (20)(21)(22)(50)(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

“…This stimulation is mediated, at least in part, by signaling through TLR2 and TLR4 and the associated activation of JNK (13-17). However, M1 activation may also be influenced by the levels of intracellular FAs, which regulate a wide variety of signaling pathways (18)(19)(20)(21)(22). These intracellular FAs exist in different pools, including free FAs, FA acyl CoAs, and inert FA moieties that are incorporated into glycerolipids, such as triacylglycerols (TGs) (23).…”

Section: Introductionmentioning

confidence: 99%

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DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation

Koliwad

Streeper²,

Monetti³

et al. 2010

J. Clin. Invest.

190

134

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Diet-induced obesity (DIO) leads to inflammatory activation of macrophages in white adipose tissue (WAT) and subsequently to insulin resistance. PPARγ agonists are antidiabetic agents known to suppress inflammatory macrophage activation and to induce expression of the triacylglycerol (TG) synthesis enzyme acyl CoA: diacylglycerol acyltransferase 1 (DGAT1) in WAT and in adipocytes. Here, we investigated in mice the relationship between macrophage lipid storage capacity and DIO-associated inflammatory macrophage activation. Mice overexpressing DGAT1 in both macrophages and adipocytes (referred to herein as aP2-Dgat1 mice) were more prone to DIO but were protected against inflammatory macrophage activation, macrophage accumulation in WAT, systemic inflammation, and insulin resistance. To assess the contribution of macrophage DGAT1 expression to this phenotype, we transplanted wild-type mice with aP2-Dgat1 BM. These mice developed DIO similar to that of control mice but retained the protection from WAT inflammation and insulin resistance seen in aP2-Dgat1 mice. In isolated macrophages, Dgat1 mRNA levels correlated directly with TG storage capacity and inversely with inflammatory activation by saturated fatty acids (FAs). Moreover, PPARγ agonists increased macrophage Dgat1 mRNA levels, and the protective effects of these agonists against FA-induced inflammatory macrophage activation were absent in macrophages isolated from Dgat1-null mice. Thus, increasing DGAT1 expression in murine macrophages increases their capacity for TG storage, protects against FA-induced inflammatory activation, and is sufficient to reduce the inflammatory and metabolic consequences of DIO. IntroductionChronic diet-induced obesity (DIO) promotes infiltration of the white adipose tissue (WAT) by monocyte-derived phagocytic and antigen-presenting cells that include macrophages and dendritic cells. These macrophages accumulate in crown-like structures (CLS) around dying or apoptotic adipocytes and change their overall polarity from a relatively antiinflammatory (M2) activation state to a more inflammatory (M1) state (1-5). The M1 activation of macrophages in WAT is linked to chronically elevated serum levels of inflammatory cytokines, such as TNF-α, that are key to the development of insulin resistance, diabetes, and atherosclerosis (6-9).Determining the molecular mechanisms that trigger M1 activation of macrophages in WAT during DIO may offer insights into the metabolic consequences of obesity. Recent evidence points to the importance of saturated fatty acids (FAs), which are systemically elevated in chronic DIO (10, 11) and stimulate M1 activation of macrophages and dendritic cells in culture (12)(13)(14)(15). This stimulation is mediated, at least in part, by signaling through TLR2 and TLR4 and the associated activation of JNK (13-17). However, M1 activation may also be influenced by the levels of intracellular FAs, which regulate a wide variety of signaling pathways (18)(19)(20)(21)(22). These intracellular FAs exist in different pools, incl...

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“…eicosanoids, diacylglycerols, lysophosphatidic acids) and ER stress, which itself can induce JNK phosphorylation and NF-κB activation in cells (20)(21)(22)(50)(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation

Koliwad

Streeper²,

Monetti³

et al. 2010

J. Clin. Invest.

190

134

View full text Add to dashboard Cite

show abstract

“…Since SCFA receptors, such as G protein coupled receptor 41 or 43 (GPR41,43), are highly expressed in both adipocytes and macrophages 18,19) , butyrate may have synergistic effects on both cell types. In addition, it is reported that FFAs act as ligands for Toll-like receptor 4 (TLR4), which plays an important role in the inflammatory response and is highly expressed in macrophages 20,21) . These findings indicate that butyrate might be applicable for its physiological and pharmacological effects 22) .…”

Section: Introductionmentioning

confidence: 99%

Butyrate Attenuates Inflammation and Lipolysis Generated by the Interaction of Adipocytes and Macrophages

Ohira

Fujioka

Katagiri

et al. 2013

JAT

180

131

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Aim: Paracrine interaction between macrophages and adipocytes in obese visceral fat tissues is thought to be a trigger of chronic inflammation. The immunomodulatory effect of the short chain fatty acid, butyric acid, has been demonstrated. We hypothesize that sodium butyrate (butyrate) attenuates inflammatory responses and lipolysis generated by the interaction of macrophages and adipocytes. Methods: Using contact or transwell co-culture methods with differentiated 3T3-L1 adipocytes and RAW264.7 macrophages, we investigated the effects of butyrate on the production of tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), and the release of free glycerol, free fatty acids (FFAs) into the medium. We also examined the activity of nuclear factor-kappaB (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs) in co-cultured macrophages, as well as lipase activity and expression in co-cultured adipocytes. Results: We found increased production of TNF-α, MCP-1, IL-6, and free glycerol, FFAs in the coculture medium, and butyrate significantly reduced them. Butyrate inhibited the phosphorylation of MAPKs, the activity of NF-κB in co-cultured macrophages, and suppressed lipase activity in co-cultured adipocytes. Lipase inhibitors significantly attenuated the production of TNF-α, MCP-1 and IL-6 in the co-culture medium as effectively as butyrate. Butyrate suppressed the protein production of adipose triglyceride lipase, hormone sensitive lipase, and fatty acid-binding protein 4 in co-cultured adipocytes. Pertussis toxin, which is known to block GPR41 completely, inhibited the antilipolysis effect of butyrate. Conclusion: Butyrate suppresses inflammatory responses generated by the interaction of adipocytes and macrophages through reduced lipolysis and inhibition of inflammatory signaling.

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“…FAs have been reported to exert their effects by modulating immune cell functions, resulting in stimulation and/or inhibition of the production of cytokines, chemokines, growth factors, reactive oxygen species (ROS), lipid mediators, and antibodies (1)(2)(3). PUFAs are thought to play an important function in the prevention and treatment of cardiovascular, inflammatory, and autoimmune diseases (4)(5)(6)(7).…”

mentioning

confidence: 99%

Suppression of superoxide anion and elastase release by C18 unsaturated fatty acids in human neutrophils

Hwang

Chang

et al. 2009

Journal of Lipid Research

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The structure-activity relationship of 18-carbon fatty acids (C 18 FAs) on human neutrophil functions and their underlying mechanism were investigated. C 18 unsaturated (U)FAs potently inhibited superoxide anion production, elastase release, and Ca 21 mobilization at concentrations of UFAs did not reduce extracellular Ba 21 entry in FMLP-and thapsigargin-activated neutrophils. In summary, the inhibition of neutrophil functions by C 18 UFAs is attributed to the blockade of Ca 21 mobilization through modulation of PMCA. We also suggest that both the free carboxy group and the number of double bonds of the C 18 UFA structure are critical to providing the potent anti-inflammatory properties in human neutrophils.-Hwang,

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Mechanisms by which fatty acids regulate leucocyte function

Cited by 65 publications

References 146 publications

DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation

DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation

Butyrate Attenuates Inflammation and Lipolysis Generated by the Interaction of Adipocytes and Macrophages

Suppression of superoxide anion and elastase release by C18 unsaturated fatty acids in human neutrophils

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