Jane Ferguson
Last active: 3/3/2020

Docosahexaenoic acid attenuates macrophage-induced inflammation and improves insulin sensitivity in adipocytes-specific differential effects between LC n-3 PUFA.

Oliver E, McGillicuddy FC, Harford KA, Reynolds CM, Phillips CM, Ferguson JF, Roche HM
J Nutr Biochem. 2012 23 (9): 1192-200

PMID: 22137266 · DOI:10.1016/j.jnutbio.2011.06.014

OBJECTIVE - Adipose tissue inflammation with immune cell recruitment plays a key role in obesity-induced insulin resistance (IR). Long-chain (LC) n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory potential; however, their individual effects on adipose IR are ill defined. We hypothesized that EPA and DHA may differentially affect macrophage-induced IR in adipocytes.

METHODS - J774.2 macrophages pretreated with EPA or DHA (50 μM for 5 days) were stimulated with lipopolysaccharide (LPS, 100 ng/ml for 30 min-48 h). Cytokine secretion profiles and activation status of macrophages were assessed by enzyme-linked immunosorbent assay and flow cytometry. Pretreated macrophages were seeded onto transwell inserts and placed over 3T3-L1 adipocytes for 24-72 h; effects on adipocyte-macrophage cytokine cross-talk and insulin-stimulated ³H-glucose transport into adipocytes were monitored.

RESULTS - DHA had more potent anti-inflammatory effects relative to EPA, with marked attenuation of LPS-induced nuclear factor (NF)κB activation and tumor necrosis factor (TNF)α secretion in macrophages. DHA specifically enhanced anti-inflammatory interleukin (IL)-10 secretion and reduced the expression of proinflammatory M1 (F4/80⁺/CD11⁺) macrophages. Co-culture of DHA-enriched macrophages with adipocytes attenuated IL-6 and TNFα secretion while enhancing IL-10 secretion. Conditioned media (CM) from DHA-enriched macrophages attenuated adipocyte NFκB activation. Adipocytes co-cultured with DHA-enriched macrophages maintained insulin sensitivity with enhanced insulin-stimulated ³H-glucose transport, GLUT4 translocation and preservation of insulin-receptor substrate-1 expression compared to co-culture with untreated macrophages. We confirmed that IL-10 expressed by DHA-enriched macrophages attenuates the CM-induced proinflammatory IR phenotype in adipocytes.

CONCLUSIONS - We demonstrate an attenuated proinflammatory phenotype of DHA-pretreated macrophages, which when co-cultured with adipocytes partially preserved insulin sensitivity.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (22)

3T3-L1 Cells Adipocytes, White Animals Anti-Inflammatory Agents, Non-Steroidal Biological Transport Cell Communication Cell Line, Transformed Coculture Techniques Culture Media, Conditioned Cytokines Docosahexaenoic Acids Eicosapentaenoic Acid Glucose Glucose Transporter Type 4 Insulin Insulin Receptor Substrate Proteins Insulin Resistance Interleukin-10 Macrophage Activation Macrophages Mice Protein Transport

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