Fiona McGillicuddy | University College Dublin (original) (raw)
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Papers by Fiona McGillicuddy
Proceedings of the …, Jan 1, 2011
The Journal of …, Jan 1, 2011
Objective: Adipose tissue inflammation with immune cell recruitment plays a key role in obesity-i... more 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 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)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 DHAenriched macrophages maintained insulin sensitivity with enhanced insulin-stimulated 3 H-glucose transport, GLUT4 translocation and preservation of insulinreceptor 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.
Proceedings of the …, Jan 1, 2011
Clinical Lipidology, Jan 1, 2010
Proceedings of the …, Jan 1, 2010
... Elizabeth Oliver1,2, Fiona McGillicuddy1, Catherine Phillips1, Sinead Toomey1 and Helen M. Ro... more ... Elizabeth Oliver1,2, Fiona McGillicuddy1, Catherine Phillips1, Sinead Toomey1 and Helen M. Roche1* 1Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Dublin 4, Republic of Ireland 2Institute of Molecular Medicine, Trinity Centre for Health ...
Proceedings of the …, Jan 1, 2010
Diabetes, Jan 1, 2009
OBJECTIVE-Adipose inflammation plays a central role in obesity-related metabolic and cardiovascul... more OBJECTIVE-Adipose inflammation plays a central role in obesity-related metabolic and cardiovascular complications. However, few human adipose-secreted proteins are known to mediate these processes. We hypothesized that microarray mRNA profiling of human adipose during evoked inflammation could identify novel adipocytokines.
Vascular …, Jan 1, 2006
Thrombospondin-1 (TSP-1) and transforming growth factor-beta1 (TGF-beta1) are both implicated in ... more Thrombospondin-1 (TSP-1) and transforming growth factor-beta1 (TGF-beta1) are both implicated in the pathogenesis of in-stent restenosis. This study evaluated the hypothesis that the HMG-CoA reductase inhibitor fluvastatin inhibits TGF-beta1 induced TSP-1 expression via inhibition of p38 mitogen activated protein kinase (MAPK) phosphorylation in human coronary artery smooth muscle cells (HCASMC) and may therefore have anti-restenosis potential. Fluvastatin significantly reduced TSP-1 mRNA and protein expression in HCASMC in a concentration-dependent manner with a significant reduction in expression observed after treatment with 0.25 microM fluvastatin. TGF-beta1 (5 ng/ml) induced phosphorylation of p38 MAPK and induced TSP-1 mRNA and protein expression in HCASMC. Fluvastatin abolished TGF-beta1-induced phosphorylation of p38 MAPK and TGF-beta1-induced TSP-1 expression. Blockade of the p38 MAPK pathway with the upstream inhibitor SB-203580 also abolished TGF-beta1-induced TSP-1 expression. We conclude that fluvastatin decreases expression of TSP-1 and abolishes the ability of TGF-beta1 to induce TSP-1 expression in HCASMC; this may be achieved by preventing signalling through the p38 MAPK pathway. Targeted delivery of fluvastatin may therefore be a useful therapeutic objective for prevention of the intimal hyperplasia associated with in-stent restenosis.
Diabetes, Jan 1, 2010
OBJECTIVE-An emerging model of metabolic syndrome and type 2 diabetes is of adipose dysfunction w... more OBJECTIVE-An emerging model of metabolic syndrome and type 2 diabetes is of adipose dysfunction with leukocyte recruitment into adipose leading to chronic inflammation and insulin resistance (IR). This study sought to explore potential mechanisms of inflammatory-induced IR in humans with a focus on adipose tissue.
Journal of Biological …, Jan 1, 2009
The Journal of Biological Chemistry Skip to main page content. ...
Proceedings of the …, Jan 1, 2011
The Journal of …, Jan 1, 2011
Objective: Adipose tissue inflammation with immune cell recruitment plays a key role in obesity-i... more 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 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)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 DHAenriched macrophages maintained insulin sensitivity with enhanced insulin-stimulated 3 H-glucose transport, GLUT4 translocation and preservation of insulinreceptor 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.
Proceedings of the …, Jan 1, 2011
Clinical Lipidology, Jan 1, 2010
Proceedings of the …, Jan 1, 2010
... Elizabeth Oliver1,2, Fiona McGillicuddy1, Catherine Phillips1, Sinead Toomey1 and Helen M. Ro... more ... Elizabeth Oliver1,2, Fiona McGillicuddy1, Catherine Phillips1, Sinead Toomey1 and Helen M. Roche1* 1Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Dublin 4, Republic of Ireland 2Institute of Molecular Medicine, Trinity Centre for Health ...
Proceedings of the …, Jan 1, 2010
Diabetes, Jan 1, 2009
OBJECTIVE-Adipose inflammation plays a central role in obesity-related metabolic and cardiovascul... more OBJECTIVE-Adipose inflammation plays a central role in obesity-related metabolic and cardiovascular complications. However, few human adipose-secreted proteins are known to mediate these processes. We hypothesized that microarray mRNA profiling of human adipose during evoked inflammation could identify novel adipocytokines.
Vascular …, Jan 1, 2006
Thrombospondin-1 (TSP-1) and transforming growth factor-beta1 (TGF-beta1) are both implicated in ... more Thrombospondin-1 (TSP-1) and transforming growth factor-beta1 (TGF-beta1) are both implicated in the pathogenesis of in-stent restenosis. This study evaluated the hypothesis that the HMG-CoA reductase inhibitor fluvastatin inhibits TGF-beta1 induced TSP-1 expression via inhibition of p38 mitogen activated protein kinase (MAPK) phosphorylation in human coronary artery smooth muscle cells (HCASMC) and may therefore have anti-restenosis potential. Fluvastatin significantly reduced TSP-1 mRNA and protein expression in HCASMC in a concentration-dependent manner with a significant reduction in expression observed after treatment with 0.25 microM fluvastatin. TGF-beta1 (5 ng/ml) induced phosphorylation of p38 MAPK and induced TSP-1 mRNA and protein expression in HCASMC. Fluvastatin abolished TGF-beta1-induced phosphorylation of p38 MAPK and TGF-beta1-induced TSP-1 expression. Blockade of the p38 MAPK pathway with the upstream inhibitor SB-203580 also abolished TGF-beta1-induced TSP-1 expression. We conclude that fluvastatin decreases expression of TSP-1 and abolishes the ability of TGF-beta1 to induce TSP-1 expression in HCASMC; this may be achieved by preventing signalling through the p38 MAPK pathway. Targeted delivery of fluvastatin may therefore be a useful therapeutic objective for prevention of the intimal hyperplasia associated with in-stent restenosis.
Diabetes, Jan 1, 2010
OBJECTIVE-An emerging model of metabolic syndrome and type 2 diabetes is of adipose dysfunction w... more OBJECTIVE-An emerging model of metabolic syndrome and type 2 diabetes is of adipose dysfunction with leukocyte recruitment into adipose leading to chronic inflammation and insulin resistance (IR). This study sought to explore potential mechanisms of inflammatory-induced IR in humans with a focus on adipose tissue.
Journal of Biological …, Jan 1, 2009
The Journal of Biological Chemistry Skip to main page content. ...