Docosahexaenoic acid decreases pro-inflammatory mediators in an in vitro murine adipocyte macrophage co-culture model

Paracrine interactions between adipocytes and macrophages contribute to chronic inflammation in obese adipose tissue. Dietary strategies to mitigate such inflammation include long-chain polyunsaturated fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, which act through PPARγ-depen...

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Published in:PloS one 2014-01, Vol.9 (1), p.e85037
Main Authors: De Boer, Anna A, Monk, Jennifer M, Robinson, Lindsay E
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adipocytes
Adipocytes - drug effects
Adipocytes - metabolism
Adiponectin
Adipose tissue
Albumin
Animals
Biology
Cell culture
Cell Line
Cellular proteins
Chemokine CCL2 - metabolism
Coculture Techniques
Cytokines
Diabetes
Diet
Docosahexaenoic acid
Docosahexaenoic Acids - pharmacology
Eicosapentaenoic Acid - pharmacology
Fatty acids
Gene expression
Genotype & phenotype
Inflammation
Insulin resistance
Interleukin 6
Interleukin-10 - metabolism
Interleukin-6 - metabolism
Macrophages
Macrophages - drug effects
Macrophages - metabolism
Medicine
Mice
NF-κB protein
Nitric-oxide synthase
Obesity
Omega 3 fatty acids
Palmitic acid
Paracrine signalling
Polarization
Polyunsaturated fatty acids
RNA
Saturated fatty acids
Transforming growth factor-b1
Tumor Necrosis Factor-alpha - metabolism
Type 2 diabetes
Unsaturated fatty acids
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creator De Boer, Anna A
Monk, Jennifer M
Robinson, Lindsay E
description Paracrine interactions between adipocytes and macrophages contribute to chronic inflammation in obese adipose tissue. Dietary strategies to mitigate such inflammation include long-chain polyunsaturated fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, which act through PPARγ-dependent and independent pathways. We utilized an in vitro co-culture model designed to mimic the ratio of macrophages:adipocytes in obese adipose tissue, whereby murine 3T3-L1 adipocytes were cultured with RAW 264.7 macrophages in direct contact, or separated by a trans-well membrane (contact-independent mechanism), with 125 µM of albumin-complexed DHA, EPA, palmitic acid (PA), or albumin alone (control). Thus, we studied the effect of physical cell contact versus the presence of soluble factors, with or without a PPARγ antagonist (T0070907) in order to elucidate putative mechanisms. After 12 hr, DHA was the most anti-inflammatory, decreasing MCP1 and IL-6 secretion in the contact system (-57%, -63%, respectively, p ≤ 0.05) with similar effects in the trans-well system. The trans-well system allowed for isolation of cell types for inflammatory mediator analysis. DHA decreased mRNA expression (p
doi_str_mv 10.1371/journal.pone.0085037
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Dietary strategies to mitigate such inflammation include long-chain polyunsaturated fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, which act through PPARγ-dependent and independent pathways. We utilized an in vitro co-culture model designed to mimic the ratio of macrophages:adipocytes in obese adipose tissue, whereby murine 3T3-L1 adipocytes were cultured with RAW 264.7 macrophages in direct contact, or separated by a trans-well membrane (contact-independent mechanism), with 125 µM of albumin-complexed DHA, EPA, palmitic acid (PA), or albumin alone (control). Thus, we studied the effect of physical cell contact versus the presence of soluble factors, with or without a PPARγ antagonist (T0070907) in order to elucidate putative mechanisms. After 12 hr, DHA was the most anti-inflammatory, decreasing MCP1 and IL-6 secretion in the contact system (-57%, -63%, respectively, p ≤ 0.05) with similar effects in the trans-well system. The trans-well system allowed for isolation of cell types for inflammatory mediator analysis. DHA decreased mRNA expression (p&lt;0.05) of Mcp1 (-7.1 fold) and increased expression of the negative regulator, Mcp1-IP (+1.5 fold). In macrophages, DHA decreased mRNA expression of pro-inflammatory M1 polarization markers (p ≤ 0.05), Nos2 (iNOS; -7 fold), Tnfα (-4.2 fold) and Nfκb (-2.3 fold), while increasing anti-inflammatory Tgfβ1 (+1.7 fold). Interestingly, the PPARγ antagonist co-administered with DHA or EPA in co-culture reduced (p ≤ 0.05) adiponectin cellular protein, without modulating other cytokines (protein or mRNA). 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Dietary strategies to mitigate such inflammation include long-chain polyunsaturated fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, which act through PPARγ-dependent and independent pathways. We utilized an in vitro co-culture model designed to mimic the ratio of macrophages:adipocytes in obese adipose tissue, whereby murine 3T3-L1 adipocytes were cultured with RAW 264.7 macrophages in direct contact, or separated by a trans-well membrane (contact-independent mechanism), with 125 µM of albumin-complexed DHA, EPA, palmitic acid (PA), or albumin alone (control). Thus, we studied the effect of physical cell contact versus the presence of soluble factors, with or without a PPARγ antagonist (T0070907) in order to elucidate putative mechanisms. After 12 hr, DHA was the most anti-inflammatory, decreasing MCP1 and IL-6 secretion in the contact system (-57%, -63%, respectively, p ≤ 0.05) with similar effects in the trans-well system. The trans-well system allowed for isolation of cell types for inflammatory mediator analysis. DHA decreased mRNA expression (p&lt;0.05) of Mcp1 (-7.1 fold) and increased expression of the negative regulator, Mcp1-IP (+1.5 fold). In macrophages, DHA decreased mRNA expression of pro-inflammatory M1 polarization markers (p ≤ 0.05), Nos2 (iNOS; -7 fold), Tnfα (-4.2 fold) and Nfκb (-2.3 fold), while increasing anti-inflammatory Tgfβ1 (+1.7 fold). Interestingly, the PPARγ antagonist co-administered with DHA or EPA in co-culture reduced (p ≤ 0.05) adiponectin cellular protein, without modulating other cytokines (protein or mRNA). Overall, our findings suggest that DHA may lessen the degree of MCP1 and IL-6 secreted from adipocytes, and may reduce the degree of M1 polarization of macrophages recruited to adipose tissue, thereby decreasing the intensity of pro-inflammatory cross-talk between adipocytes and macrophages in obese adipose tissue.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24465472</pmid><doi>10.1371/journal.pone.0085037</doi><tpages>e85037</tpages><oa>free_for_read</oa></addata></record>
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subjects 3T3-L1 Cells
Adipocytes
Adipocytes - drug effects
Adipocytes - metabolism
Adiponectin
Adipose tissue
Albumin
Animals
Biology
Cell culture
Cell Line
Cellular proteins
Chemokine CCL2 - metabolism
Coculture Techniques
Cytokines
Diabetes
Diet
Docosahexaenoic acid
Docosahexaenoic Acids - pharmacology
Eicosapentaenoic Acid - pharmacology
Fatty acids
Gene expression
Genotype & phenotype
Inflammation
Insulin resistance
Interleukin 6
Interleukin-10 - metabolism
Interleukin-6 - metabolism
Macrophages
Macrophages - drug effects
Macrophages - metabolism
Medicine
Mice
NF-κB protein
Nitric-oxide synthase
Obesity
Omega 3 fatty acids
Palmitic acid
Paracrine signalling
Polarization
Polyunsaturated fatty acids
RNA
Saturated fatty acids
Transforming growth factor-b1
Tumor Necrosis Factor-alpha - metabolism
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title Docosahexaenoic acid decreases pro-inflammatory mediators in an in vitro murine adipocyte macrophage co-culture model
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