TY  - JOUR
  - Oliver, E.,McGillicuddy, F. C.,Harford, K. A.,Reynolds, C. M.,Phillips, C. M.,Ferguson, J. F.,Roche, H. M.
  - 2012
  - September
  - Docosahexaenoic acid attenuates macrophage-induced inflammation and improves insulin sensitivity in adipocytes-specific differential effects between LC n-3 PUFA
  - Validated
  - ()
  - 23
  - 99
  - 1192
  - 2001192
  - 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 muM 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 (3)H-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)kappaB activation and tumor necrosis factor (TNF)alpha 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 TNFalpha secretion while enhancing IL-10 secretion. Conditioned media (CM) from DHA-enriched macrophages attenuated adipocyte NFkappaB activation. Adipocytes co-cultured with DHA-enriched macrophages maintained insulin sensitivity with enhanced insulin-stimulated (3)H-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.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 muM 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 (3)H-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)kappaB activation and tumor necrosis factor (TNF)alpha 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 TNFalpha secretion while enhancing IL-10 secretion. Conditioned media (CM) from DHA-enriched macrophages attenuated adipocyte NFkappaB activation. Adipocytes co-cultured with DHA-enriched macrophages maintained insulin sensitivity with enhanced insulin-stimulated (3)H-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.
  - 1873-4847 (Electronic) 09
  - http://www.ncbi.nlm.nih.gov/pubmed/22137266http://www.ncbi.nlm.nih.gov/pubmed/22137266
DA  - 2012/09
ER  - 

@article{V180957364,
   = {Oliver,  E. and McGillicuddy,  F. C. and Harford,  K. A. and Reynolds,  C. M. and Phillips,  C. M. and Ferguson,  J. F. and Roche,  H. M. },
   = {2012},
   = {September},
   = {Docosahexaenoic acid attenuates macrophage-induced inflammation and improves insulin sensitivity in adipocytes-specific differential effects between LC n-3 PUFA},
   = {Validated},
   = {()},
   = {23},
   = {99},
  pages = {1192--2001192},
   = {{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 muM 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 (3)H-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)kappaB activation and tumor necrosis factor (TNF)alpha 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 TNFalpha secretion while enhancing IL-10 secretion. Conditioned media (CM) from DHA-enriched macrophages attenuated adipocyte NFkappaB activation. Adipocytes co-cultured with DHA-enriched macrophages maintained insulin sensitivity with enhanced insulin-stimulated (3)H-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.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 muM 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 (3)H-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)kappaB activation and tumor necrosis factor (TNF)alpha 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 TNFalpha secretion while enhancing IL-10 secretion. Conditioned media (CM) from DHA-enriched macrophages attenuated adipocyte NFkappaB activation. Adipocytes co-cultured with DHA-enriched macrophages maintained insulin sensitivity with enhanced insulin-stimulated (3)H-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.}},
  issn = {1873-4847 (Electronic) 09},
   = {http://www.ncbi.nlm.nih.gov/pubmed/22137266http://www.ncbi.nlm.nih.gov/pubmed/22137266},
  source = {IRIS}
}